TY - JOUR
AU - Hopkinson, Andrew
AB - Abstract CD34 is a transmembrane phosphoglycoprotein, first identified on hematopoietic stem and progenitor cells. Clinically, it is associated with the selection and enrichment of hematopoietic stem cells for bone marrow transplants. Due to these historical and clinical associations, CD34 expression is almost ubiquitously related to hematopoietic cells, and it is a common misconception that CD34-positive (CD34+) cells in nonhematopoietic samples represent hematopoietic contamination. The prevailing school of thought states that multipotent mesenchymal stromal cells (MSC) do not express CD34. However, strong evidence demonstrates CD34 is expressed not only by MSC but by a multitude of other nonhematopoietic cell types including muscle satellite cells, corneal keratocytes, interstitial cells, epithelial progenitors, and vascular endothelial progenitors. In many cases, the CD34+ cells represent a small proportion of the total cell population and also indicate a distinct subset of cells with enhanced progenitor activity. Herein, we explore common traits between cells that express CD34, including associated markers, morphology and differentiation potential. We endeavor to highlight key similarities between CD34+ cells, with a focus on progenitor activity. A common function of CD34 has yet to be elucidated, but by analyzing and understanding links between CD34+ cells, we hope to be able to offer an insight into the overlapping properties of cells that express CD34. Stem Cells 2014;32:1380–1389 CD34, Stem cell, Progenitor, Mesenchymal, Stromal, Epithelial, Endothelial Introduction CD34 is predominantly regarded as a marker of hematopoietic stem cells (HSC) and hematopoietic progenitor cells. However, CD34 is now also established as a marker of several other nonhematopoietic cell types, including vascular endothelial progenitors [1] and embryonic fibroblasts [2]. Accumulating evidence demonstrates CD34 expression on several other cell types, including multipotent mesenchymal stromal cells (MSC), interstitial dendritic cells, and epithelial progenitors [3-6], but there remains limited recognition of the role of CD34-positive (CD34+) cells outside of each individual specialty. Despite consistent evidence of expression by many cell types, there is still a misconception that CD34 represents a cell of hematopoietic origin, and experimentally, CD34+ cells are often regarded as hematopoietic contamination and subsequently disregarded. This review presents evidence establishing CD34 as a general marker of progenitor cells. We explore common traits, such as marker expression, morphology and differentiation potential, and endeavor to draw focus toward the many, disparate cell types that express CD34, and in the process highlight key similarities. CD34 expression across different cell types and the associated implications has not previously been presented, although selected literature has reviewed expression within individual cell groups. Although a common function of CD34 has yet to be elucidated, analyzing and understanding the links between cells offers an insight into the role of CD34 in identifying progenitor cells from many tissue types. A summary of the properties of all the CD34+ cell types discussed in this review can be found in Table 1. Summary of different CD34+ cell types CD34+ cell type . Associated markers . Differentiation potential . Properties . Reference . HSC and progenitors HLA-DR, CD38, CD117 (c-kit), CD45, CD133 Hematopoietic cells, cardiomyocytes, hepatocytes Large nucleus, little cytoplasm, high proliferative capacity [7, 8] MSC Stro-1, CD73, CD90, CD105, CD146, CD29, CD44, CD271 Adipogenic, osteogenic, chondrogenic, myogenic, angiogenic CD34+ MSC form a higher proportion of CFU-f colonies than CD34−. CD34+ MSC exhibit a high proliferative capacity. Fibroblastic cells [9-13] Muscle satellite cells CD56, Myf5, Desmin, M-cadherin, CD90, CD106, Flk-1, VEGFR, MyoD, CD146 Myogenic, adipogenic, osteogenic, chondrogenic The CD56+CD34+ population may represent a more primitive or pluripotent stem cell. In vivo, CD34+ cells are located near the basal lamina. Small and round [14-17] Keratocytes CD34, CD133, l-selectin, keratocan, ALDH Fibroblastic, myofibroblastic, adipogenic, osteogenic, chondrogenic, corneal epithelial, corneal endothelial Dendritic morphology. In vitro population acquires an MSC phenotype [18-21] Interstitial cells CD117, vimentin, Desmin, Connexin-43, PDGFRβ Not yet fully elucidated Triangular or spindle-shaped with large nucleus and long cytoplasmic processes. CD34+ population may have a stem cell/progenitor role in the bladder, intestine, and reproductive organs [22-24] Fibrocyte CD45, CD80, CD86, MHC class I and II Fibroblastic, myofibroblastic, adipogenic, osteogenic, chondrogenic Small spindle shape. CD34 is lost in culture and upon maturation [25-27] Epithelial progenitors CD49f, CD10, CD146, CD71, S100a4, Dkk3, CD133, CD117, ALDH, CD90 Dermal epithelial cells, neural mesenchymal Predominantly described in HF niche in skin [28-33] Endothelial cells CD146, VE-cadherin, CD133, CD117, CD14, CD31 Angiogenesis Elongated with filopodia. Lack tight junctions. CD34 is present on luminal membrane processes and is expressed on filopodia during in vivo angiogenesis. Quiescent in vivo/low proliferation activity [1, 34, 35] CD34+ cell type . Associated markers . Differentiation potential . Properties . Reference . HSC and progenitors HLA-DR, CD38, CD117 (c-kit), CD45, CD133 Hematopoietic cells, cardiomyocytes, hepatocytes Large nucleus, little cytoplasm, high proliferative capacity [7, 8] MSC Stro-1, CD73, CD90, CD105, CD146, CD29, CD44, CD271 Adipogenic, osteogenic, chondrogenic, myogenic, angiogenic CD34+ MSC form a higher proportion of CFU-f colonies than CD34−. CD34+ MSC exhibit a high proliferative capacity. Fibroblastic cells [9-13] Muscle satellite cells CD56, Myf5, Desmin, M-cadherin, CD90, CD106, Flk-1, VEGFR, MyoD, CD146 Myogenic, adipogenic, osteogenic, chondrogenic The CD56+CD34+ population may represent a more primitive or pluripotent stem cell. In vivo, CD34+ cells are located near the basal lamina. Small and round [14-17] Keratocytes CD34, CD133, l-selectin, keratocan, ALDH Fibroblastic, myofibroblastic, adipogenic, osteogenic, chondrogenic, corneal epithelial, corneal endothelial Dendritic morphology. In vitro population acquires an MSC phenotype [18-21] Interstitial cells CD117, vimentin, Desmin, Connexin-43, PDGFRβ Not yet fully elucidated Triangular or spindle-shaped with large nucleus and long cytoplasmic processes. CD34+ population may have a stem cell/progenitor role in the bladder, intestine, and reproductive organs [22-24] Fibrocyte CD45, CD80, CD86, MHC class I and II Fibroblastic, myofibroblastic, adipogenic, osteogenic, chondrogenic Small spindle shape. CD34 is lost in culture and upon maturation [25-27] Epithelial progenitors CD49f, CD10, CD146, CD71, S100a4, Dkk3, CD133, CD117, ALDH, CD90 Dermal epithelial cells, neural mesenchymal Predominantly described in HF niche in skin [28-33] Endothelial cells CD146, VE-cadherin, CD133, CD117, CD14, CD31 Angiogenesis Elongated with filopodia. Lack tight junctions. CD34 is present on luminal membrane processes and is expressed on filopodia during in vivo angiogenesis. Quiescent in vivo/low proliferation activity [1, 34, 35] Abbreviations: ALDH, aldehyde dehydrogenase; CD, cluster of differentiation; CFU-F, colony forming units fibroblast; Flk-1, fetal liver kinase-1; HF, hair follicle; HLA-DR, human leukocyte antigen-DR; HSC, hematopoietic stem cells; MSC, multipotent mesenchymal stromal cells; Myf5, myogenic factor 5; MyoD, myogenic differentiation 1; MHC, major histocompatibility complex; PDGFRβ, platelet derived growth factor receptor β; VEGFR, vascular endothelial growth factor receptor. Open in new tab Summary of different CD34+ cell types CD34+ cell type . Associated markers . Differentiation potential . Properties . Reference . HSC and progenitors HLA-DR, CD38, CD117 (c-kit), CD45, CD133 Hematopoietic cells, cardiomyocytes, hepatocytes Large nucleus, little cytoplasm, high proliferative capacity [7, 8] MSC Stro-1, CD73, CD90, CD105, CD146, CD29, CD44, CD271 Adipogenic, osteogenic, chondrogenic, myogenic, angiogenic CD34+ MSC form a higher proportion of CFU-f colonies than CD34−. CD34+ MSC exhibit a high proliferative capacity. Fibroblastic cells [9-13] Muscle satellite cells CD56, Myf5, Desmin, M-cadherin, CD90, CD106, Flk-1, VEGFR, MyoD, CD146 Myogenic, adipogenic, osteogenic, chondrogenic The CD56+CD34+ population may represent a more primitive or pluripotent stem cell. In vivo, CD34+ cells are located near the basal lamina. Small and round [14-17] Keratocytes CD34, CD133, l-selectin, keratocan, ALDH Fibroblastic, myofibroblastic, adipogenic, osteogenic, chondrogenic, corneal epithelial, corneal endothelial Dendritic morphology. In vitro population acquires an MSC phenotype [18-21] Interstitial cells CD117, vimentin, Desmin, Connexin-43, PDGFRβ Not yet fully elucidated Triangular or spindle-shaped with large nucleus and long cytoplasmic processes. CD34+ population may have a stem cell/progenitor role in the bladder, intestine, and reproductive organs [22-24] Fibrocyte CD45, CD80, CD86, MHC class I and II Fibroblastic, myofibroblastic, adipogenic, osteogenic, chondrogenic Small spindle shape. CD34 is lost in culture and upon maturation [25-27] Epithelial progenitors CD49f, CD10, CD146, CD71, S100a4, Dkk3, CD133, CD117, ALDH, CD90 Dermal epithelial cells, neural mesenchymal Predominantly described in HF niche in skin [28-33] Endothelial cells CD146, VE-cadherin, CD133, CD117, CD14, CD31 Angiogenesis Elongated with filopodia. Lack tight junctions. CD34 is present on luminal membrane processes and is expressed on filopodia during in vivo angiogenesis. Quiescent in vivo/low proliferation activity [1, 34, 35] CD34+ cell type . Associated markers . Differentiation potential . Properties . Reference . HSC and progenitors HLA-DR, CD38, CD117 (c-kit), CD45, CD133 Hematopoietic cells, cardiomyocytes, hepatocytes Large nucleus, little cytoplasm, high proliferative capacity [7, 8] MSC Stro-1, CD73, CD90, CD105, CD146, CD29, CD44, CD271 Adipogenic, osteogenic, chondrogenic, myogenic, angiogenic CD34+ MSC form a higher proportion of CFU-f colonies than CD34−. CD34+ MSC exhibit a high proliferative capacity. Fibroblastic cells [9-13] Muscle satellite cells CD56, Myf5, Desmin, M-cadherin, CD90, CD106, Flk-1, VEGFR, MyoD, CD146 Myogenic, adipogenic, osteogenic, chondrogenic The CD56+CD34+ population may represent a more primitive or pluripotent stem cell. In vivo, CD34+ cells are located near the basal lamina. Small and round [14-17] Keratocytes CD34, CD133, l-selectin, keratocan, ALDH Fibroblastic, myofibroblastic, adipogenic, osteogenic, chondrogenic, corneal epithelial, corneal endothelial Dendritic morphology. In vitro population acquires an MSC phenotype [18-21] Interstitial cells CD117, vimentin, Desmin, Connexin-43, PDGFRβ Not yet fully elucidated Triangular or spindle-shaped with large nucleus and long cytoplasmic processes. CD34+ population may have a stem cell/progenitor role in the bladder, intestine, and reproductive organs [22-24] Fibrocyte CD45, CD80, CD86, MHC class I and II Fibroblastic, myofibroblastic, adipogenic, osteogenic, chondrogenic Small spindle shape. CD34 is lost in culture and upon maturation [25-27] Epithelial progenitors CD49f, CD10, CD146, CD71, S100a4, Dkk3, CD133, CD117, ALDH, CD90 Dermal epithelial cells, neural mesenchymal Predominantly described in HF niche in skin [28-33] Endothelial cells CD146, VE-cadherin, CD133, CD117, CD14, CD31 Angiogenesis Elongated with filopodia. Lack tight junctions. CD34 is present on luminal membrane processes and is expressed on filopodia during in vivo angiogenesis. Quiescent in vivo/low proliferation activity [1, 34, 35] Abbreviations: ALDH, aldehyde dehydrogenase; CD, cluster of differentiation; CFU-F, colony forming units fibroblast; Flk-1, fetal liver kinase-1; HF, hair follicle; HLA-DR, human leukocyte antigen-DR; HSC, hematopoietic stem cells; MSC, multipotent mesenchymal stromal cells; Myf5, myogenic factor 5; MyoD, myogenic differentiation 1; MHC, major histocompatibility complex; PDGFRβ, platelet derived growth factor receptor β; VEGFR, vascular endothelial growth factor receptor. Open in new tab Structure and Function of CD34 CD34 is a transmembrane phosphoglycoprotein, first identified in 1984 on hematopoietic stem and progenitor cells [36]. It has a molecular weight of approximately 115 kDa and possesses an extracellular domain that is heavily sialylated, O-linked glycosylated, and contains some N-linked glycosylation sites. There is a single transmembrane helix and a cytoplasmic tail that contains PDZ (PSD-95-Dlg-ZO-1)-domain binding motifs [3, 37]. The most commonly described ligand for CD34 is l-Selectin (CD62L), however, the adapter protein CrkL, known for adhesion regulation, also binds CD34 [38, 39]. Although the structure of CD34 is well-investigated, there is still relatively little known about its function. Studies in hematopoietic cells suggest roles in cytoadhesion and regulation of cell differentiation and proliferation [40, 41]. Lymphocytes exhibit l-selectin-mediated adhesion to CD34 surface proteins in the vascular endothelium [38, 42] and in addition, it has been hypothesized that CD34 plays a role in trafficking of HSC to niches within the bone marrow (BM) [41]. However in contrast, CD34 has also been associated with blocking of adhesion, particularly involving mast cells [43]. CD34 and Hematopoietic Cells The expression of CD34 on hematopoietic progenitors and the properties of these cells have been discussed in depth previously [7, 44, 45] and are not covered in detail in this review. In clinical practice, CD34 expression is evaluated to ensure rapid engraftment in BM transplants and can also be used as a selective marker in cell sorting to enrich a population of immature hematopoietic cells [46, 47]. Although sometimes assumed to be solely a stem cell marker, the detection of CD34 in BM or blood samples represents a hematopoietic stem/progenitor mix, of which the majority of cells are progenitor [44]. Human HSC are further separated from CD34+ progenitor cells by low expression of CD90 and a lack of expression of CD38, human leukocyte antigen-DR, and a panel of mature hematopoietic lineage markers (lin−) [7]. CD34+ HSC are able to differentiate into all cells of the hematopoietic lineage and have a high proliferative capacity [7, 8]. Evidence suggests that CD34+ HSC and progenitors have the ability to differentiate in vivo into other lineages, including respiratory epithelial cells [48], hepatocytes [49], and cardiomyocytes [50]. Thus far, the properties of CD34+ HSC have not been directly linked to the properties of CD34+ non-HSC. CD34 and Stromal Cells Multipotent MSC MSC are found in most adult tissues and are a prevalent and versatile cell type, studied extensively for regenerative medicine applications [51]. Although their in vitro mesenchymal differentiation potential is well-reported, MSC are also frequently associated with other properties including paracrine wound healing, niche forming abilities, immune privilege, and immunomodulation [52, 53]. Nomenclature of MSC is a controversial topic, with differing opinions on whether cells should be identified as mesenchymal stem cells or multipotent mesenchymal stromal cells, among many other names [54]. In this review, we use the term multipotent mesenchymal stromal cells but include a broad range of references that refer generically to mesenchymal stem and progenitor cells. This section includes research on MSC from different tissue sources and discusses both freshly isolated and culture expanded MSC. Two recent reviews have discussed the expression of CD34 on MSC, both with an emphasis on adipose-derived MSC [4, 55]. While Scherberich et al. [55] concentrated on the structure and function of CD34 in relation to MSC, Lin et al. [4] challenged the opinion that CD34 is a negative marker of MSC. The latter review discussed evidence demonstrating that CD34 was an important marker in early MSC research, highlighting research by Simmons and Torok-Storb showing that freshly isolated, CD34+ BM MSC form greater proportions of fibroblastic colonies (colony forming units fibroblast) than their CD34− counterparts [9]. The review also made the observation that CD34+ MSC were originally used in screening for additional MSC immunogens, leading to the identification of Stro-1 [56]. They concluded that CD34 should be considered a positive marker of MSC, with a particular association to vasculature and suggested that these cells be known as vascular stem cells [4]. While Lin et al. highlights several key issues in the definition of an MSC, the review only briefly touches upon a connection between CD34 and progenitor cells. This same review was also critical of the position paper, published in 2006, by the International Society for Cellular Therapy (ISCT) [57], which outlined a minimal criteria for cells to be considered MSC. These criteria, based predominantly on MSC extracted from BM, describe a plastic-adherent, culture expanded cell population and have subsequently been widely adopted by the research community. One ISCT criterion states that to be considered MSC, a cell population must be largely negative for CD34 (≤2% of the population). This is due to the consideration that CD34 is a marker of hematopoietic cells, alongside a number of previous studies that show an absence of CD34 in cultured MSC [58-60]. In support of the ISCT, establishing well-defined criteria has created a clear benchmark for the depiction of MSC populations, allowing more accurate and reproducible comparisons between research groups. MSC populations demonstrate high levels of heterogeneity and this diversity exists not only within different tissue sources but also between MSC from a single source and clonal MSC [60, 61]. Hence, prior to the establishment of these criteria, many disparate cell types were described as MSC, leading to uncertainty over MSC properties and characteristics. However, in unifying and defining characterization, it is almost certain that stromal progenitors expressing markers that are considered negative, or not included in the ISCT criteria, are being overlooked by researchers, and more importantly, actively removed when following these guidelines. Although prevailing opinion states that MSC are CD34−, in vitro characterization predominantly takes place following culture, usually after several passages. Consequently, this is not representative of the in vivo or initially extracted cell phenotype. Freshly extracted stromal cells, from various tissues, have been shown to contain CD34+ cells [9-11, 63]. The expression of CD34 has been demonstrated more extensively on MSC isolated from sources other than BM, such as adipose tissue, and therefore is more widely accepted by researchers in these areas [10, 61, 64]. CD34+ MSC are present immediately following extraction but rapidly diminish in numbers after a short time in culture [12, 13, 65]. For example, when analyzing adipose-derived MSC at P0, Mitchell et al. described an average of 59.2% of adherent cells expressing CD34, which decreased to 5% at passage 2 and subsequently disappeared [64]. This change in CD34 expression upon culture is also mirrored in changes of expression of other surface antigens. Freshly extracted adipose MSC also show low expression of CD73, CD90, and CD105 that increase upon culture; this is of interest due to the ISCT classification of these as definitive MSC markers [10, 64]. There are also decreases in expression of other markers associated with MSC, such as CD106, CD146, and CD271 [12, 13, 64, 66]. This change in MSC phenotype upon culture is perhaps indicative of a differentiation process or response to environmental changes. CD34+ cells represent a proportion of the total MSC population, and this subset of cells possesses distinct characteristics. CD34 expression is associated with high colony forming efficiency and long-term proliferative capacity [9, 12, 63]. CD34+ MSC have been associated with typical MSC markers, alongside differentially expressed markers such as CD271 and Stro-1, and markers commonly related to other cell types including CD45 and CD133 [10, 12, 13, 41, 42, 67, 68]. CD34+ MSC have been shown to possess a greater propensity for endothelial transdifferentiation [14, 69]. CD34 is also found on embryonic stem cell derived MSC, further suggesting it to be a marker of early human MSC [15]. Muscle Satellite Cells CD34 is commonly used as a marker of both human and mouse muscle satellite cells, also known as muscle stem cells [16, 70]. Muscle satellite cells are small, stromal progenitor cells that give rise to mature skeletal muscle cells. In vivo, muscle satellite cells are quiescent, unless activated to provide myonuclei for myofibers, by increased weight-bearing exercise or trauma. Activation of these cells, also considered to be differentiation, corresponds to a complete downregulation of CD34 [71]. CD34 has been suggested to play a fundamental role in the regulation of muscle progenitor cell differentiation and establishment and maintenance of a satellite cell population [71]. CD34 is not expressed on all muscle satellite cells but is used in identification alongside other markers including CD56 [16, 17]. Developmentally, the earliest known myogenic precursors do not express CD34 and during muscle development CD34 expression is first detected with the appearance of committed muscle satellite cells [72]. This, alongside the simultaneous expression of myogenic markers such as Myf5 and M-cadherin, is suggestive of CD34+ satellite cells demonstrating a prior commitment to the myogenic fate [71]. Alternative evidence proposes that CD34+ cells have the potential to be more than myogenic precursors. Distinct MSC-like cells, that demonstrate in vitro mesenchymal differentiation, have been identified in muscle satellite locations by characterizing CD34 expression [73]. Similar to MSC, CD34 expression on muscle satellite cells does not persist during culture and disappears as the cells differentiate. It has been suggested that CD34+ cells residing in the interstitial spaces of muscle are related to endothelial cells, due to the expression profile CD56+CD34+CD144+ [18]. These myoendothelial cells show an enhanced ability to regenerate muscle, compared to cells that express only myogenic or endothelial markers in an in vivo mouse model. They also differentiate in vitro down the osteogenic and chondrogenic lineages. The different observed properties of muscle satellite cells may be explained by the presence of distinct subsets of CD34+ cells, with distinct differentiation potentials [17]. The markers that are coexpressed alongside CD34 have an impact on differentiation. For example, CD34+ cells that coexpress the endothelial marker CD31 display angiogenic differentiation. However, CD34+CD31− cell populations demonstrate greater potential to differentiate down the adipogenic and myogenic lineage [17]. Corneal Keratocytes The corneal stroma is populated with quiescent cells known as keratocytes, which exhibit a dendritic morphology with extensive cellular contacts [19]. Similar to muscle satellite cells, CD34 is a well-established marker for quiescent keratocytes in vivo (Fig. 1) [74, 75]. As a result of corneal trauma, keratocytes adjacent to the wound take on a more fibroblastic phenotype and CD34 expression rapidly disappears, as cells become “activated” [20]. Upon activation, they shift to a fibroblastic phenotype and are associated with stromal tissue remodeling and scar formation [76]. Activation also occurs in vitro, when keratocytes are cultured on tissue culture plastic, particularly in serum-containing medium [65, 77]. Keratocyte transformation to the fibroblast phenotype was previously thought to be irreversible in vitro, but recent evidence demonstrates that careful recapitulation of the niche-like environment and tailoring of culture conditions has the potential to revert fibroblastic cells back to a native keratocyte phenotype [78-80]. However, it has yet to be investigated whether CD34 expression is restored. Open in new tabDownload slide CD34 expression by keratocytes. (A): Immunofluorescence showing CD34 expression by keratocytes in a section of human cornea, counterstained with DAPI. Scale bar = 500 μm. (B–G): Keratocyte phenotype after in vitro culture. Human keratocytes were extracted from the corneal stroma and cultured for 5 days in Medium 199 containing 20% fetal bovine serum. (B–D): Immunocytochemistry identifying individual cells expressing CD34, among cells expressing CD105. (E–G): Keratocytes in culture also express markers associated with MSC, such as CD90 and CD73. All images counterstained with Hoechst 33258. Scale bar = 46 μm. Open in new tabDownload slide CD34 expression by keratocytes. (A): Immunofluorescence showing CD34 expression by keratocytes in a section of human cornea, counterstained with DAPI. Scale bar = 500 μm. (B–G): Keratocyte phenotype after in vitro culture. Human keratocytes were extracted from the corneal stroma and cultured for 5 days in Medium 199 containing 20% fetal bovine serum. (B–D): Immunocytochemistry identifying individual cells expressing CD34, among cells expressing CD105. (E–G): Keratocytes in culture also express markers associated with MSC, such as CD90 and CD73. All images counterstained with Hoechst 33258. Scale bar = 46 μm. The function of CD34 expression in keratocytes has not yet been elucidated, although it has been speculated that CD34 plays roles in regulation of differentiation, adhesion, and quiescence [75]. Although it has been suggested that CD34+ keratocytes are of hematopoietic origin [81], these cells do not form hematopoietic colonies when cultured in semisolid medium and CD34+ cells from these cultures display a plastic adherent, dendritic morphology [65] . Although CD34+ cells disappear during in vitro culture, they can still be seen in early cultures, when cultured in medium 199 (Fig. 1B). These cells also express typical stromal markers such as CD105, CD90, and CD73 (Fig. 1C–1G). In vitro, keratocytes have been shown to display characteristics of MSC [21, 82], and after several passages, when CD34 has disappeared, conform to the requisite ISCT criteria [65]. Therefore, it has been hypothesized that the keratocyte is an MSC progenitor found in the corneal stroma [65, 83]. Additionally, recent investigations have revealed that CD34+ keratocytes possess the ability to transdifferentiate into corneal epithelial [77] and endothelial cells [22, 74]. This has led to the hypothesis that CD34 is a marker for a tissue-specific progenitor that resides in the stroma, which could give rise to all corneal lineages and MSC. Interstitial Cells and Fibrocytes CD34+ stromal cells have been described in organs including the thyroid, dermis, tonsils, uterus, and testes [84]. CD34+ cells in these cases are termed dendritic interstitial cells or fibrocytes. Although their function remains unclear, these cells display similar properties to CD34+ MSC, keratocytes, and muscle satellite cells, and it has been suggested that these cells function as progenitor cells for specific tissues. The CD34+ interstitial cells of Cajal (ICC) are mesenchymal in origin and were first identified in the gastrointestinal (GI) tract [85]. The prevailing belief is that ICC are responsible for modulating smooth muscle contraction through electrical and chemical signaling as pacemaker cells. However, the discovery of ICC in other tissues, including the pancreas, myocardium, bladder, urethra, and blood vessels, has brought into question the functional role of these cells [86]. Although not all ICC express CD34, immunoreactivity has been shown in a subset of ICC in the GI tract in mice and humans [86]. In humans, CD34+ populations have been described in the human detrusor muscle of the bladder, uterus, and fallopian tubes [23, 24]. Investigations have identified a possible role for CD34+ ICC as uncommitted progenitor cells [25]. Moreover, ICC in the bladder of mice showed colocalization of c-kit and CD34 [26] and authors have suggested a functional relationship between CD34+ ICC and mast cells. This supports the notion that CD34 expression relates to plasticity of the ICC cell type and a progenitor function. Fibrocytes are mesenchymal progenitor cells that are often considered distinct from MSC. Despite this, they are quiescent cells that circulate in the bloodstream and upon trauma are recruited to the site of injury, where the cells play roles in inflammation and wound healing [27, 87]. These cells have been shown to produce myofibroblastic, fibroblastic, adipogenic, chondrogenic, and osteogenic phenotypes in vitro [27, 28]. Fibrocytes are currently not recognized as MSC due to their cell surface marker profile which includes markers associated with leukocytes, including CD34, CD45, CD80, CD86, and major histocompatibility complex class I and II [27, 28]. As with the aforementioned stromal cells, CD34 expression disappears during in vitro culture and in vivo upon maturity and differentiation [87]. In common with other stromal cells, it has been suggested that both keratocytes and fibrocytes are derived from leukocytes due to a CD34+CD45+ cell surface marker profile [81]. CD34 and Epithelial Cells The expression of CD34 by epithelial progenitors in the skin is widely accepted [29, 88]. In vivo, each unit of epithelium contains a hair follicle (HF) and within the HF there is a stem cell niche that maintains the epithelial layers of the skin. Trauma to the epidermis results in migration of stem cells from this niche to the injury site. Within the niche there are populations of multipotent epithelial stem cells and a subpopulation of these cells is CD34+ [29, 89]. The location of the CD34+ cells in the HF is one of contention, depending on species. The majority of studies have been conducted on mice and in these cases the CD34+ population resides in the outer root sheath (ORS) bulge, alongside other recognized stem cells [6, 29]. Human HFs are considerably more difficult to study, due to small size and low cell numbers. However, indications show that the CD34+ cells are not located in the ORS bulge, but are below the bulge zone, in the suprabulbar region [89-91]. In humans, CD34+ cells have also been identified in the skin between the HF, in the basal interfollicular epidermis, but these cells are less well-investigated [92]. It has been suggested that because the CD34+ cells are not present in the adult human ORS bulge, with the majority of other stem cells, they are the progeny of bulge stem cells [92]. HFs are constantly cycling through stages of active hair growth (anagen), destruction (catagen), and rest (telogen). During these stages, cell surface marker expression and phenotype within the HF is altered [6]. CD34 expression is seen in human HFs during anagen but not during catagen and telogen [89]. The authors suggest that this indicates that CD34 function relates only to epithelial cells that are proliferating and also relates to adhesion of the root sheath cells to the surrounding stroma. It is worth noting that although human CD34+ cells are not located in the bulge with other stem cells, they are located in the area of the HF that demonstrates the most clonogenic activity [30]. In human HFs, cells that express CD34 do not express cytokeratin 15 (CK15), another commonly used marker of epithelial progenitor cells [31], suggesting either more than one population of progenitor cells or a hierarchy of cells at different stages of differentiation [89]. CD34+ cells of the HF are multipotent and able to generate a fully stratified epidermis [6, 32]. There is some evidence to show that HF stem cells, including CD34+ cells, may be pluripotent, demonstrating transdifferentiation into neural and mesenchymal lineages [33, 93]. The majority of research into CD34 expression in epithelial cells has been performed on skin tissue. However, there is a population of CD34+ stem cells residing in the epithelial ducts of the salivary gland [94, 95]. These cells retain their proliferative ability when cultured in 3D structures known as salispheres and demonstrate differentiation into cells and structures reminiscent of the salivary gland. There are also some links between CD34+ stromal cells and epithelial cells. CD34+ keratocytes have been shown to express the epithelial cell marker CK3 [96], and CD34+ cells from human fetal liver express biliary epithelial markers CK7, CK8, and CK18 [97]. CD34 and Endothelial Cells CD34 is widely regarded as a marker of vascular endothelial progenitor cells [1, 98]. These BM-derived cells are found circulating in peripheral blood [99] and their usefulness in proangiogenic therapies has been extensively researched [98, 99]. The properties of CD34+ endothelial cells are often linked with hematopoietic cells, as both cell types can be isolated from peripheral blood using CD34 as an antigen. CD34+ cells isolated from peripheral blood have been studied for use in neovascularization therapies [100] and furthermore have shown ability to differentiate into cardiomyocytes [50] and osteoblasts [34]. A review published several years ago by Matsumoto et al. [35] discussed a possible overlap between endothelial progenitor cells and osteoblasts. There is a circulating CD34+ population of endothelial/skeletal progenitor cells, thought to originate in BM, capable of differentiating into both osteoblasts and endothelial cells. Investigations are ongoing using the circulating CD34+ cells to treat cases of nonunion fractures, which often suffer from delayed healing times due to inadequate blood supply around the injury site. There is a subset of noncirculating adult endothelial cells that are also CD34+, most notably located within smaller blood vessels, while most endothelial cells in larger veins and arteries are CD34− [1]. In contrast to the typical cobblestone morphology of endothelial cells, CD34+ cells are more elongated and lack tight junctions [101]. CD34 expression is predominantly found on the luminal membrane of cellular processes but may also be seen on the abluminal membrane of cells found at the tips of vascular sprouts [1, 102]. In addition, CD34+ endothelial cells are quiescent and are thought to be involved in migration and adhesion [1]. Human umbilical vein endothelial cells (HUVEC) are CD34+ in vivo, however, when cultured in vitro, expression is lost after several passages and only a small population of CD34+ cells are retained [1]. CD34+ HUVEC have distinct morphological characteristics, including numerous filopodia [101]. Angiogenic stimuli provokes migration of these cells, and it has been proposed that this CD34+ subpopulation is homologous to sprouting tip cells, a specialized type of endothelial cell present at the leading edge during in vivo angiogenesis [101]. CD34 is strongly expressed on the filopodia of these tip cells at sites of active angiogenesis and evidence yet again emphasizes the important functional role for CD34 in progenitor cell activity. CD34 Antibody Selection Careful selection of the antibody used for CD34 sorting and identification is of utmost importance during investigations. Some CD34 monoclonal antibodies (mAbs) select for epitopes that are sensitive to cleavage with neuraminidase (sialidase) and glycoprotease [103]. Therefore, they are dependent on sialic acid residues remaining on the antigen. For this reason, an epitope classification for CD34 mAbs was devised, as seen in Table 2. There are over 30 different mAbs for CD34 targeting different epitopes, and antibody clone used by studies discussed in this review can be seen in Table 2. The most commonly used clones are MY10, a class Ib mAb, that is partially dependent on the presence of sialic acid residues and QBEnd10, a class II mAB, that has been shown to successfully detect both sialylated and desialylated CD34 [103]. The QBEnd10 clone is the antibody of choice for immunohistochemical protocols as it is resistant to denaturation and as the epitope is at the N-terminus of the CD34 molecule it is ideally suited to selection protocols such as fluorescence-activated cell sorting and magnetic-activated cell sorting. Class III epitopes, such as 8G12 retain high specificity for all glycoforms of the CD34 antigen and so are suitable for many protocols including flow cytometry and immunofluorescence [103]. Polyclonal antibodies should be avoided for CD34 sorting and immunoblotting due to the possibilities of nonspecific labeling and high variation between antibody batches. CD34 antibody selection: epitope specificity and clones Epitope class . Clone . Cell type . Assays performed . Reference . Ia. Sensitive to neuraminidase and glycoprotease 12.8 Hematopoietic cells, MSC, endothelial progenitors Immunoblots, immunostaining, FACS [19, 47] BI.3C5 MSC, keratocytes, endothelial progenitors Immunoblots, immunostaining, FACS [1, 9, 75] Ib. Partially sensitive to neuraminidase and glycoprotease ICH3 MSC, keratocytes, endothelial progenitors Immunoblots, immunostaining, FACS [1, 9, 75, 102] MY10 Hematopoietic cells, MSC, interstitial cells, endothelial progenitors Immunoblots, immunostaining, FACS, Western blots [1, 5, 9, 36, 39, 56, 84] II. Resistant to neuraminidase and sensitive to glycoprotease QBEnd10 MSC, muscle satellite cells, keratocytes, interstitial cells, HF epithelial progenitors, endothelial progenitors. Immunoblots, immunostaining, flow cytometry [1, 16, 23, 25, 65, 77, 86, 89, 101, 102] III. Resistant to neuraminidase and glycoprotease 563 HF epithelial progenitors Immunostaining [90] 581 Muscle satellite cells, keratocytes Immunostaining, flow cytometry [16, 75] 8G12 Muscle satellite cells, haematopoietic cells, MSC Immunostaining, flow cytometry, FACS [8, 12, 40, 44, 62, 64, 73] TUK3 Endothelial progenitors Immunoblots [1] 115.2 Endothelial progenitors Immunoblots [1] Monoclonal (clone not stated) MSC Immunostaining, flow cytometry [10, 58, 59, 63, 69] Polyclonal HF epithelial Flow cytometry [91] Antibody type not stated MSC, muscle satellite cells, keratocytes, HF epithelial progenitors, salivary epithelial progenitors, endothelial progenitors Immunostaining, flow cytometry, FACS [13-15, 18, 21, 30, 34, 60, 67, 68, 70, 74, 82, 83, 92, 94] Epitope class . Clone . Cell type . Assays performed . Reference . Ia. Sensitive to neuraminidase and glycoprotease 12.8 Hematopoietic cells, MSC, endothelial progenitors Immunoblots, immunostaining, FACS [19, 47] BI.3C5 MSC, keratocytes, endothelial progenitors Immunoblots, immunostaining, FACS [1, 9, 75] Ib. Partially sensitive to neuraminidase and glycoprotease ICH3 MSC, keratocytes, endothelial progenitors Immunoblots, immunostaining, FACS [1, 9, 75, 102] MY10 Hematopoietic cells, MSC, interstitial cells, endothelial progenitors Immunoblots, immunostaining, FACS, Western blots [1, 5, 9, 36, 39, 56, 84] II. Resistant to neuraminidase and sensitive to glycoprotease QBEnd10 MSC, muscle satellite cells, keratocytes, interstitial cells, HF epithelial progenitors, endothelial progenitors. Immunoblots, immunostaining, flow cytometry [1, 16, 23, 25, 65, 77, 86, 89, 101, 102] III. Resistant to neuraminidase and glycoprotease 563 HF epithelial progenitors Immunostaining [90] 581 Muscle satellite cells, keratocytes Immunostaining, flow cytometry [16, 75] 8G12 Muscle satellite cells, haematopoietic cells, MSC Immunostaining, flow cytometry, FACS [8, 12, 40, 44, 62, 64, 73] TUK3 Endothelial progenitors Immunoblots [1] 115.2 Endothelial progenitors Immunoblots [1] Monoclonal (clone not stated) MSC Immunostaining, flow cytometry [10, 58, 59, 63, 69] Polyclonal HF epithelial Flow cytometry [91] Antibody type not stated MSC, muscle satellite cells, keratocytes, HF epithelial progenitors, salivary epithelial progenitors, endothelial progenitors Immunostaining, flow cytometry, FACS [13-15, 18, 21, 30, 34, 60, 67, 68, 70, 74, 82, 83, 92, 94] Abbreviations: FACS, fluorescence-activated cell sorting; HF, hair follicle; MSC, multipotent mesenchymal stromal cells. Open in new tab CD34 antibody selection: epitope specificity and clones Epitope class . Clone . Cell type . Assays performed . Reference . Ia. Sensitive to neuraminidase and glycoprotease 12.8 Hematopoietic cells, MSC, endothelial progenitors Immunoblots, immunostaining, FACS [19, 47] BI.3C5 MSC, keratocytes, endothelial progenitors Immunoblots, immunostaining, FACS [1, 9, 75] Ib. Partially sensitive to neuraminidase and glycoprotease ICH3 MSC, keratocytes, endothelial progenitors Immunoblots, immunostaining, FACS [1, 9, 75, 102] MY10 Hematopoietic cells, MSC, interstitial cells, endothelial progenitors Immunoblots, immunostaining, FACS, Western blots [1, 5, 9, 36, 39, 56, 84] II. Resistant to neuraminidase and sensitive to glycoprotease QBEnd10 MSC, muscle satellite cells, keratocytes, interstitial cells, HF epithelial progenitors, endothelial progenitors. Immunoblots, immunostaining, flow cytometry [1, 16, 23, 25, 65, 77, 86, 89, 101, 102] III. Resistant to neuraminidase and glycoprotease 563 HF epithelial progenitors Immunostaining [90] 581 Muscle satellite cells, keratocytes Immunostaining, flow cytometry [16, 75] 8G12 Muscle satellite cells, haematopoietic cells, MSC Immunostaining, flow cytometry, FACS [8, 12, 40, 44, 62, 64, 73] TUK3 Endothelial progenitors Immunoblots [1] 115.2 Endothelial progenitors Immunoblots [1] Monoclonal (clone not stated) MSC Immunostaining, flow cytometry [10, 58, 59, 63, 69] Polyclonal HF epithelial Flow cytometry [91] Antibody type not stated MSC, muscle satellite cells, keratocytes, HF epithelial progenitors, salivary epithelial progenitors, endothelial progenitors Immunostaining, flow cytometry, FACS [13-15, 18, 21, 30, 34, 60, 67, 68, 70, 74, 82, 83, 92, 94] Epitope class . Clone . Cell type . Assays performed . Reference . Ia. Sensitive to neuraminidase and glycoprotease 12.8 Hematopoietic cells, MSC, endothelial progenitors Immunoblots, immunostaining, FACS [19, 47] BI.3C5 MSC, keratocytes, endothelial progenitors Immunoblots, immunostaining, FACS [1, 9, 75] Ib. Partially sensitive to neuraminidase and glycoprotease ICH3 MSC, keratocytes, endothelial progenitors Immunoblots, immunostaining, FACS [1, 9, 75, 102] MY10 Hematopoietic cells, MSC, interstitial cells, endothelial progenitors Immunoblots, immunostaining, FACS, Western blots [1, 5, 9, 36, 39, 56, 84] II. Resistant to neuraminidase and sensitive to glycoprotease QBEnd10 MSC, muscle satellite cells, keratocytes, interstitial cells, HF epithelial progenitors, endothelial progenitors. Immunoblots, immunostaining, flow cytometry [1, 16, 23, 25, 65, 77, 86, 89, 101, 102] III. Resistant to neuraminidase and glycoprotease 563 HF epithelial progenitors Immunostaining [90] 581 Muscle satellite cells, keratocytes Immunostaining, flow cytometry [16, 75] 8G12 Muscle satellite cells, haematopoietic cells, MSC Immunostaining, flow cytometry, FACS [8, 12, 40, 44, 62, 64, 73] TUK3 Endothelial progenitors Immunoblots [1] 115.2 Endothelial progenitors Immunoblots [1] Monoclonal (clone not stated) MSC Immunostaining, flow cytometry [10, 58, 59, 63, 69] Polyclonal HF epithelial Flow cytometry [91] Antibody type not stated MSC, muscle satellite cells, keratocytes, HF epithelial progenitors, salivary epithelial progenitors, endothelial progenitors Immunostaining, flow cytometry, FACS [13-15, 18, 21, 30, 34, 60, 67, 68, 70, 74, 82, 83, 92, 94] Abbreviations: FACS, fluorescence-activated cell sorting; HF, hair follicle; MSC, multipotent mesenchymal stromal cells. Open in new tab Almost all methods of cell surface marker analysis involve the binding of antibodies to an antigen. Antigen–antibody interactions are noncovalent and can be reversible; therefore, it is important to validate an experiment carefully. Key proteins of interest can be interrogated using multiple methods, such as using an alternative antibody, technique or analysis of gene transcription. To characterize a cell population it is essential to develop a comprehensive characterization process comprising of a profile of markers, both surface and intracellular, functional assays and, as in the case of stem cells, interrogation of their differentiation potentials. Conclusion CD34 is a cell surface marker that is expressed by a broad range of cells including hematopoietic, stromal, epithelial, and endothelial cells. Although the function of CD34 as a surface antigen is still unknown, it has been linked to inhibition or facilitation of adhesion, cell proliferation, and regulation of differentiation [40, 41, 55, 103]. This review focused on the use of CD34 to identify cells from diverse tissues that have comparable properties (Table 3). The discernible link between all CD34+ cell types is progenitor and stem cell activity, and in many cases, the CD34+ population of cells shows a more potent or pronounced differentiation capacity. Research alludes to a correlation between cell plasticity and CD34 expression, with loss of CD34, alongside other cell surface antigens, suggesting lineage commitment from the more positive progenitor cell. Many of these cells also demonstrate a quiescent state in vivo, until activated to differentiate. Although all the cell types discussed throughout this review express CD34, they do not all display identical properties. Many coexpress tissue-specific markers alongside CD34, suggesting that the presence of CD34 may indicate a specific progenitor for that tissue. Evidence for this is certainly apparent in muscle satellite cells, keratocytes, and epithelial progenitors. However, this does not necessarily limit the differentiation capacity of the cells in vitro, with many of the CD34+ cells linked by transdifferentiation ability. Comparable properties of CD34+ cells Comparable properties of CD34+ cells . Described in: . Potential stem/progenitor cell population HSC, MSC, muscle satellite cells, keratocytes, interstitial cells, fibrocytes, HF epithelial stem cells, vascular endothelial progenitors Quiescent in vivo Muscle satellite cells, keratocytes, interstitial cells, fibrocytes Greater CFU-F capacity and high proliferative capacity in vitro HSC, MSC, HF epithelial stem cells Loss of CD34 expression upon “activation” or differentiation either in vivo or upon in vitro culture MSC, muscle satellite cells, keratocytes, fibrocytes, HF epithelial stem cells Coexpression with tissue specific markers Muscle satellite cells, keratocytes, interstitial cells, HF epithelial stem cells, salivary gland stem cells, vascular endothelial progenitors Transdifferentiation potential HSC, MSC, muscle satellite cells, keratocytes, HF epithelial stem cells, vascular endothelial progenitors Comparable properties of CD34+ cells . Described in: . Potential stem/progenitor cell population HSC, MSC, muscle satellite cells, keratocytes, interstitial cells, fibrocytes, HF epithelial stem cells, vascular endothelial progenitors Quiescent in vivo Muscle satellite cells, keratocytes, interstitial cells, fibrocytes Greater CFU-F capacity and high proliferative capacity in vitro HSC, MSC, HF epithelial stem cells Loss of CD34 expression upon “activation” or differentiation either in vivo or upon in vitro culture MSC, muscle satellite cells, keratocytes, fibrocytes, HF epithelial stem cells Coexpression with tissue specific markers Muscle satellite cells, keratocytes, interstitial cells, HF epithelial stem cells, salivary gland stem cells, vascular endothelial progenitors Transdifferentiation potential HSC, MSC, muscle satellite cells, keratocytes, HF epithelial stem cells, vascular endothelial progenitors Abbreviations: CD, cluster of differentiation; CFU-F, colony forming units fibroblast; HF, hair follicle; HSC, hematopoietic stem cells; MSC, multipotent mesenchymal stromal cells. Open in new tab Comparable properties of CD34+ cells Comparable properties of CD34+ cells . Described in: . Potential stem/progenitor cell population HSC, MSC, muscle satellite cells, keratocytes, interstitial cells, fibrocytes, HF epithelial stem cells, vascular endothelial progenitors Quiescent in vivo Muscle satellite cells, keratocytes, interstitial cells, fibrocytes Greater CFU-F capacity and high proliferative capacity in vitro HSC, MSC, HF epithelial stem cells Loss of CD34 expression upon “activation” or differentiation either in vivo or upon in vitro culture MSC, muscle satellite cells, keratocytes, fibrocytes, HF epithelial stem cells Coexpression with tissue specific markers Muscle satellite cells, keratocytes, interstitial cells, HF epithelial stem cells, salivary gland stem cells, vascular endothelial progenitors Transdifferentiation potential HSC, MSC, muscle satellite cells, keratocytes, HF epithelial stem cells, vascular endothelial progenitors Comparable properties of CD34+ cells . Described in: . Potential stem/progenitor cell population HSC, MSC, muscle satellite cells, keratocytes, interstitial cells, fibrocytes, HF epithelial stem cells, vascular endothelial progenitors Quiescent in vivo Muscle satellite cells, keratocytes, interstitial cells, fibrocytes Greater CFU-F capacity and high proliferative capacity in vitro HSC, MSC, HF epithelial stem cells Loss of CD34 expression upon “activation” or differentiation either in vivo or upon in vitro culture MSC, muscle satellite cells, keratocytes, fibrocytes, HF epithelial stem cells Coexpression with tissue specific markers Muscle satellite cells, keratocytes, interstitial cells, HF epithelial stem cells, salivary gland stem cells, vascular endothelial progenitors Transdifferentiation potential HSC, MSC, muscle satellite cells, keratocytes, HF epithelial stem cells, vascular endothelial progenitors Abbreviations: CD, cluster of differentiation; CFU-F, colony forming units fibroblast; HF, hair follicle; HSC, hematopoietic stem cells; MSC, multipotent mesenchymal stromal cells. Open in new tab Although CD34 may be one marker that is useful in identifying progenitor populations, a single marker alone is not appropriate for the characterization of a cell type. The expression of CD34 by all cell types discussed throughout the review may not be exclusive. Due to a lack of cohesive research, we cannot yet identify another marker that appears on all cells, but markers such as CD90, CD117 (c-kit), CD146, and CD133 have been indicated on more than one cell type. To fully characterize a population of stem cells it is most likely that a specific marker profile would be required, alongside clonal assays, differentiation assays and functional profiling. The culture and propagation of adherent CD34+ cells in vitro is challenging. This is conceivably due to the association of CD34 with quiescence and adhesion, and the loss of CD34 expression upon differentiation. Culture on tissue culture plastic and in serum-containing medium creates an environment dissimilar to the in vivo environment, forcing the cells to proliferate and differentiate, subsequently losing CD34. If CD34+ cells are to be investigated in vitro, more thought, specialized culture conditions and optimization is required to recapitulate an environment more similar to the in vivo niche. By compiling this review, we would like to propose that CD34 is considered as a surface antigen suitable for the selection of subpopulations of progenitor cells from larger cell populations, including mesenchymal cells, and is not associated only with hematopoietic and endothelial cells. Recognizing CD34 as a progenitor marker will allow further research into this distinct subset of cells, which potentially possess a pronounced differentiation capacity. If culture and propagation techniques for these cells can be optimized, CD34+ cells from many tissue types may represent a source of progenitor cells that can be exploited clinically in regenerative medicine strategies. Acknowledgements This work was supported by grants from The Royal College of Surgeons Edinburgh and Fight for Sight. S.E.D. is supported by funding from the EPSRC Doctoral Training Centre in Regenerative Medicine. The authors would like to thank Mr Owen McIntosh for discussions and assistance with proof reading. Author Contributions L.E.S. and M.J.B.: conception and design, collection and assembly of data, data analysis and interpretation, and manuscript writing; S.E.D.: data analysis and interpretation and manuscript writing; H.S.D. and A.H.: financial support, final approval of manuscript. Disclosure of Potential Conflicts of Interest The authors indicate no potential conflicts of interest. References 1 Fina L , Molgaard HV, Robertson D et al. Expression of the CD34 gene in vascular endothelial cells . Blood 1990 ; 75 : 2417 – 2426 . Google Scholar Crossref Search ADS PubMed WorldCat 2 Brown J , Greaves MF, Molgaard HV. The gene encoding the stem cell antigen, CD34, is conserved in mouse and expressed in haemopoietic progenitor cell lines, brain, and embryonic fibroblasts . Int Immunol 1991 ; 3 : 175 – 184 . Google Scholar Crossref Search ADS PubMed WorldCat 3 Nielsen JS , McNagny KM. Novel functions of the CD34 family . J Cell Sci 2008 ; 121 : 3683 – 3692 . Google Scholar Crossref Search ADS PubMed WorldCat 4 Lin CS , Ning H, Lin G et al. Is CD34 truly a negative marker for mesenchymal stromal cells? Cytotherapy 2012 ; 14 : 1159 – 1163 . Google Scholar Crossref Search ADS PubMed WorldCat 5 Nakayama H , Enzan H, Miyazaki E et al. Differential expression of CD34 in normal colorectal tissue, peritumoral inflammatory tissue, and tumour stroma . J Clin Pathol 2000 ; 53 : 626 – 629 . Google Scholar Crossref Search ADS PubMed WorldCat 6 Blanpain C , Lowry WE, Geoghegan A et al. Self-renewal, multipotency, and the existence of two cell populations within an epithelial stem cell niche . Cell 2004 ; 118 : 635 – 648 . Google Scholar Crossref Search ADS PubMed WorldCat 7 Huss R . Isolation of primary and immortalized CD34-hematopoietic and mesenchymal stem cells from various sources . Stem Cells 2000 ; 18 : 1 – 9 . Google Scholar Crossref Search ADS PubMed WorldCat 8 Servida F , Soligo D, Caneva L et al. Functional and morphological characterization of immunomagnetically selected CD34+ hematopoietic progenitor cells . Stem Cells 1996 ; 14 : 430 – 438 . Google Scholar Crossref Search ADS PubMed WorldCat 9 Simmons PJ , Torok-Storb B. CD34 expression by stromal precursors in normal human adult bone marrow . Blood 1991 ; 78 : 2848 – 2853 . Google Scholar Crossref Search ADS PubMed WorldCat 10 Yoshimura K , Shigeura T, Matsumoto D et al. Characterization of freshly isolated and cultured cells derived from the fatty and fluid portions of liposuction aspirates . J Cell Physiol 2006 ; 208 : 64 – 76 . Google Scholar Crossref Search ADS PubMed WorldCat 11 Ferraro GA , De Francesco F, Nicoletti G et al. Human adipose CD34(+) CD90(+) stem cells and collagen scaffold constructs grafted in vivo fabricate loose connective and adipose tissues . J Cell Biochem 2013 ; 114 : 1039 – 1049 . Google Scholar Crossref Search ADS PubMed WorldCat 12 Quirici N , Soligo D, Bossolasco P et al. Isolation of bone marrow mesenchymal stem cells by anti-nerve growth factor receptor antibodies . Exp Hematol 2002 ; 30 : 783 – 791 . Google Scholar Crossref Search ADS PubMed WorldCat 13 Kuci S , Kuci Z, Kreyenberg H et al. CD271 antigen defines a subset of multipotent stromal cells with immunosuppressive and lymphohematopoietic engraftment-promoting properties . Haematologica 2010 ; 95 : 651 – 659 . Google Scholar Crossref Search ADS PubMed WorldCat 14 De Francesco F , Tirino V, Desiderio V et al. Human CD34/CD90 ASCs are capable of growing as sphere clusters, producing high levels of VEGF and forming capillaries . PLoS One 2009 ; 4 : e6537 . Google Scholar Crossref Search ADS PubMed WorldCat 15 Kopher RA , Penchev VR, Islam MS et al. Human embryonic stem cell-derived CD34+ cells function as MSC progenitor cells . Bone 2010 ; 47 : 718 – 728 . Google Scholar Crossref Search ADS PubMed WorldCat 16 Sinanan AC , Hunt NP, Lewis MP. Human adult craniofacial muscle-derived cells: Neural-cell adhesion-molecule (NCAM; CD56)-expressing cells appear to contain multipotential stem cells . Biotechnol Appl Biochem 2004 ; 40 : 25 – 34 . Google Scholar PubMed OpenURL Placeholder Text WorldCat 17 Dupas T , Rouaud T, Rouger K et al. Fetal muscle contains different CD34+ cell subsets that distinctly differentiate into adipogenic, angiogenic and myogenic lineages . Stem Cell Res 2011 ; 7 : 230 – 243 . Google Scholar Crossref Search ADS PubMed WorldCat 18 Zheng B , Cao B, Crisan M et al. Prospective identification of myogenic endothelial cells in human skeletal muscle . Nat Biotechnol 2007 ; 25 : 1025 – 1034 . Google Scholar Crossref Search ADS PubMed WorldCat 19 Poole CA , Brookes NH, Clover GM. Keratocyte networks visualised in the living cornea using vital dyes . J Cell Sci 1993 ; 106 ( Pt 2 ): 685 – 691 . Google Scholar PubMed OpenURL Placeholder Text WorldCat 20 West-Mays JA , Dwivedi DJ. The keratocyte: Corneal stromal cell with variable repair phenotypes . Int J Biochem Cell Biol 2006 ; 38 : 1625 – 1631 . Google Scholar Crossref Search ADS PubMed WorldCat 21 Polisetty N , Fatima A, Madhira SL et al. Mesenchymal cells from limbal stroma of human eye . Mol Vis 2008 ; 14 : 431 – 442 . Google Scholar PubMed OpenURL Placeholder Text WorldCat 22 Hatou S , Yoshida S, Higa K et al. Functional corneal endothelium derived from corneal stroma stem cells of neural crest origin by retinoic acid and Wnt/beta-catenin signaling . Stem Cells Dev 2013 ; 22 : 828 – 839 . Google Scholar Crossref Search ADS PubMed WorldCat 23 Rasmussen H , Hansen A, Smedts F et al. CD34-positive interstitial cells of the human detrusor . APMIS 2007 ; 115 : 1260 – 1266 . Google Scholar Crossref Search ADS PubMed WorldCat 24 Popescu LM , Ciontea SM, Cretoiu D. Interstitial Cajal-like cells in human uterus and fallopian tube . Ann N Y Acad Sci 2007 ; 1101 : 139 – 165 . Google Scholar Crossref Search ADS PubMed WorldCat 25 Popescu LM , Ciontea SM, Cretoiu D et al. Novel type of interstitial cell (Cajal-like) in human fallopian tube . J Cell Mol Med 2005 ; 9 : 479 – 523 . Google Scholar Crossref Search ADS PubMed WorldCat 26 Yu W , Zeidel ML, Hill WG. Cellular expression profile for interstitial cells of cajal in bladder - a cell often misidentified as myocyte or myofibroblast . PLoS One 2012 ; 7 : e48897 . Google Scholar Crossref Search ADS PubMed WorldCat 27 Keeley EC , Mehrad B, Strieter RM. The role of circulating mesenchymal progenitor cells (fibrocytes) in the pathogenesis of fibrotic disorders . Thromb Haemost 2009 ; 101 : 613 – 618 . Google Scholar Crossref Search ADS PubMed WorldCat 28 Choi YH , Burdick MD, Strieter RM. Human circulating fibrocytes have the capacity to differentiate osteoblasts and chondrocytes . Int J Biochem Cell Biol 2010 ; 42 : 662 – 671 . Google Scholar Crossref Search ADS PubMed WorldCat 29 Tumbar T , Guasch G, Greco V et al. Defining the epithelial stem cell niche in skin . Science 2004 ; 303 : 359 – 363 . Google Scholar Crossref Search ADS PubMed WorldCat 30 Rochat A , Kobayashi K, Barrandon Y. Location of stem cells of human hair follicles by clonal analysis . Cell 1994 ; 76 : 1063 – 1073 . Google Scholar Crossref Search ADS PubMed WorldCat 31 Waseem A , Dogan B, Tidman N et al. Keratin 15 expression in stratified epithelia: Downregulation in activated keratinocytes . J Invest Dermatol 1999 ; 112 : 362 – 369 . Google Scholar Crossref Search ADS PubMed WorldCat 32 Gutierrez-Rivera A , Pavon-Rodriguez A, Jimenez-Acosta F et al. Functional characterization of highly adherent CD34+ keratinocytes isolated from human skin . Exp Dermatol 2010 ; 19 : 685 – 688 . Google Scholar Crossref Search ADS PubMed WorldCat 33 Sieber-Blum M , Grim M, Hu YF et al. Pluripotent neural crest stem cells in the adult hair follicle . Dev Dyn 2004 ; 231 : 258 – 269 . Google Scholar Crossref Search ADS PubMed WorldCat 34 Tondreau T , Meuleman N, Delforge A et al. Mesenchymal stem cells derived from CD133-positive cells in mobilized peripheral blood and cord blood: Proliferation, Oct4 expression, and plasticity . Stem Cells 2005 ; 23 : 1105 – 1112 . Google Scholar Crossref Search ADS PubMed WorldCat 35 Matsumoto T , Kuroda R, Mifune Y et al. Circulating endothelial/skeletal progenitor cells for bone regeneration and healing . Bone 2008 ; 43 : 434 – 439 . Google Scholar Crossref Search ADS PubMed WorldCat 36 Civin CI , Strauss LC, Brovall C et al. Antigenic analysis of hematopoiesis. III. A hematopoietic progenitor cell surface antigen defined by a monoclonal antibody raised against KG-1a cells . J Immunol 1984 ; 133 : 157 – 165 . Google Scholar PubMed OpenURL Placeholder Text WorldCat 37 Krause DS , Ito T, Fackler MJ et al. Characterization of murine CD34, a marker for hematopoietic progenitor and stem cells . Blood 1994 ; 84 : 691 – 701 . Google Scholar Crossref Search ADS PubMed WorldCat 38 Baumheter S , Singer MS, Henzel W et al. Binding of L-selectin to the vascular sialomucin CD34 . Science 1993 ; 262 : 436 – 438 . Google Scholar Crossref Search ADS PubMed WorldCat 39 Felschow DM , McVeigh ML, Hoehn GT et al. The adapter protein CrkL associates with CD34 . Blood 2001 ; 97 : 3768 – 3775 . Google Scholar Crossref Search ADS PubMed WorldCat 40 . Healy L , May G, Gale K et al. The stem cell antigen CD34 functions as a regulator of hemopoietic cell adhesion . Proc Natl Acad Sci USA 1995 ; 92 : 12240 – 12244 . Google Scholar Crossref Search ADS PubMed WorldCat 41 Nielsen JS , McNagny KM. CD34 is a key regulator of hematopoietic stem cell trafficking to bone marrow and mast cell progenitor trafficking in the periphery . Microcirculation 2009 ; 16 : 487 – 496 . Google Scholar Crossref Search ADS PubMed WorldCat 42 Butcher EC , Picker LJ. Lymphocyte homing and homeostasis . Science 1996 ; 272 : 60 – 66 . Google Scholar Crossref Search ADS PubMed WorldCat 43 Drew E , Merzaban JS, Seo W et al. CD34 and CD43 inhibit mast cell adhesion and are required for optimal mast cell reconstitution . Immunity 2005 ; 22 : 43 – 57 . Google Scholar Crossref Search ADS PubMed WorldCat 44 Majeti R , Park CY, Weissman IL. Identification of a hierarchy of multipotent hematopoietic progenitors in human cord blood . Cell Stem Cell 2007 ; 1 : 635 – 645 . Google Scholar Crossref Search ADS PubMed WorldCat 45 Ivanovic Z . Hematopoietic stem cells in research and clinical applications: The "CD34 issue" . World J Stem Cells 2010 ; 2 : 18 – 23 . Google Scholar Crossref Search ADS PubMed WorldCat 46 Berardi AC , Wang A, Levine JD et al. Functional isolation and characterization of human hematopoietic stem cells . Science 1995 ; 267 : 104 – 108 . Google Scholar Crossref Search ADS PubMed WorldCat 47 Berenson RJ , Bensinger WI, Hill RS et al. Engraftment after infusion of CD34+ marrow cells in patients with breast cancer or neuroblastoma . Blood 1991 ; 77 : 1717 – 1722 . Google Scholar Crossref Search ADS PubMed WorldCat 48 Mao Q , Chu S, Ghanta S et al. Ex vivo expanded human cord blood-derived hematopoietic progenitor cells induce lung growth and alveolarization in injured newborn lungs . Respir Res 2013 ; 14 : 37 . Google Scholar Crossref Search ADS PubMed WorldCat 49 Jang YY , Collector MI, Baylin SB et al. Hematopoietic stem cells convert into liver cells within days without fusion . Nat Cell Biol 2004 ; 6 : 532 – 539 . Google Scholar Crossref Search ADS PubMed WorldCat 50 Zhang S , Wang D, Estrov Z et al. Both cell fusion and transdifferentiation account for the transformation of human peripheral blood CD34-positive cells into cardiomyocytes in vivo . Circulation 2004 ; 110 : 3803 – 3807 . Google Scholar Crossref Search ADS PubMed WorldCat 51 da Silva Meirelles L , Chagastelles PC, Nardi NB. Mesenchymal stem cells reside in virtually all post-natal organs and tissues . J Cell Sci 2006 ; 119 : 2204 – 2213 . Google Scholar Crossref Search ADS PubMed WorldCat 52 Phinney DG , Prockop DJ. Concise review: Mesenchymal stem/multipotent stromal cells: The state of transdifferentiation and modes of tissue repair—Current views . Stem Cells 2007 ; 25 : 2896 – 2902 . Google Scholar Crossref Search ADS PubMed WorldCat 53 Chamberlain G , Fox J, Ashton B et al. Concise review: Mesenchymal stem cells: Their phenotype, differentiation capacity, immunological features, and potential for homing . Stem Cells 2007 ; 25 : 2739 – 2749 . Google Scholar Crossref Search ADS PubMed WorldCat 54 Horwitz EM , Le Blanc K, Dominici M et al. Clarification of the nomenclature for MSC: The International Society for Cellular Therapy position statement . Cytotherapy 2005 ; 7 : 393 – 395 . Google Scholar Crossref Search ADS PubMed WorldCat 55 Scherberich A , Di Maggio ND, McNagny KM. A familiar stranger: CD34 expression and putative functions in SVF cells of adipose tissue . World J Stem Cells 2013 ; 5 : 1 – 8 . Google Scholar Crossref Search ADS PubMed WorldCat 56 Simmons PJ , Torok-Storb B. Identification of stromal cell precursors in human bone marrow by a novel monoclonal antibody, STRO-1 . Blood 1991 ; 78 : 55 – 62 . Google Scholar Crossref Search ADS PubMed WorldCat 57 Dominici M , Le Blanc K, Mueller I et al. Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement . Cytotherapy 2006 ; 8 : 315 – 317 . Google Scholar Crossref Search ADS PubMed WorldCat 58 Pittenger MF , Mackay AM, Beck SC et al. Multilineage potential of adult human mesenchymal stem cells . Science 1999 ; 284 : 143 – 147 . Google Scholar Crossref Search ADS PubMed WorldCat 59 Zuk PA , Zhu M, Ashjian P et al. Human adipose tissue is a source of multipotent stem cells . Mol Biol Cell 2002 ; 13 : 4279 – 4295 . Google Scholar Crossref Search ADS PubMed WorldCat 60 Wagner W , Wein F, Seckinger A et al. Comparative characteristics of mesenchymal stem cells from human bone marrow, adipose tissue, and umbilical cord blood . Exp Hematol 2005 ; 33 : 1402 – 1416 . Google Scholar Crossref Search ADS PubMed WorldCat 61 Phinney DG , Sensebe L. Mesenchymal stromal cells: Misconceptions and evolving concepts . Cytotherapy 2013 ; 15 : 140 – 145 . Google Scholar Crossref Search ADS PubMed WorldCat 62 Gronthos S , Franklin DM, Leddy HA et al. Surface protein characterization of human adipose tissue-derived stromal cells . J Cell Physiol 2001 ; 189 : 54 – 63 . Google Scholar Crossref Search ADS PubMed WorldCat 63 Waller EK , Olweus J, Lund-Johansen F et al. The "common stem cell" hypothesis reevaluated: Human fetal bone marrow contains separate populations of hematopoietic and stromal progenitors . Blood 1995 ; 85 : 2422 – 2435 . Google Scholar Crossref Search ADS PubMed WorldCat 64 Mitchell JB , McIntosh K, Zvonic S et al. Immunophenotype of human adipose-derived cells: Temporal changes in stromal-associated and stem cell-associated markers . Stem Cells 2006 ; 24 : 376 – 385 . Google Scholar Crossref Search ADS PubMed WorldCat 65 Branch MJ , Hashmani K, Dhillon P et al. Mesenchymal stem cells in the human corneal limbal stroma . Invest Ophthalmol Vis Sci 2012 ; 53 : 5109 – 5116 . Google Scholar Crossref Search ADS PubMed WorldCat 66 Halfon S , Abramov N, Grinblat B et al. Markers distinguishing mesenchymal stem cells from fibroblasts are downregulated with passaging . Stem Cells Dev 2011 ; 20 : 53 – 66 . Google Scholar Crossref Search ADS PubMed WorldCat 67 Ferraro GA , De Francesco F, Nicoletti G et al. Human adipose CD34+ CD90+ stem cells and collagen scaffold constructs grafted in vivo fabricate loose connective and adipose tissues . J Cell Biochem 2013 ; 114 : 1039 – 1049 . Google Scholar Crossref Search ADS PubMed WorldCat 68 Kaiser S , Hackanson B, Follo M et al. BM cells giving rise to MSC in culture have a heterogeneous CD34 and CD45 phenotype . Cytotherapy 2007 ; 9 : 439 – 450 . Google Scholar Crossref Search ADS PubMed WorldCat 69 Miranville A , Heeschen C, Sengenes C et al. Improvement of postnatal neovascularization by human adipose tissue-derived stem cells . Circulation 2004 ; 110 : 349 – 355 . Google Scholar Crossref Search ADS PubMed WorldCat 70 Lee JY , Qu-Petersen Z, Cao B et al. Clonal isolation of muscle-derived cells capable of enhancing muscle regeneration and bone healing . J Cell Biol 2000 ; 150 : 1085 – 1100 . Google Scholar Crossref Search ADS PubMed WorldCat 71 Beauchamp JR , Heslop L, Yu DS et al. Expression of CD34 and Myf5 defines the majority of quiescent adult skeletal muscle satellite cells . J Cell Biol 2000 ; 151 : 1221 – 1234 . Google Scholar Crossref Search ADS PubMed WorldCat 72 Cossu G , Molinaro M, Pacifici M. Differential response of satellite cells and embryonic myoblasts to a tumor promoter . Dev Biol 1983 ; 98 : 520 – 524 . Google Scholar Crossref Search ADS PubMed WorldCat 73 Lecourt S , Marolleau JP, Fromigue O et al. Characterization of distinct mesenchymal-like cell populations from human skeletal muscle in situ and in vitro . Exp Cell Res 2010 ; 316 : 2513 – 2526 . Google Scholar Crossref Search ADS PubMed WorldCat 74 Perrella G , Brusini P, Spelat R et al. Expression of haematopoietic stem cell markers, CD133 and CD34 on human corneal keratocytes . Br J Ophthalmol 2007 ; 91 : 94 – 99 . Google Scholar Crossref Search ADS PubMed WorldCat 75 Joseph A , Hossain P, Jham S et al. Expression of CD34 and l-selectin on human corneal keratocytes . Invest Ophthalmol Vis Sci 2003 ; 44 : 4689 – 4692 . Google Scholar Crossref Search ADS PubMed WorldCat 76 Funderburgh JL , Mann MM, Funderburgh ML. Keratocyte phenotype mediates proteoglycan structure: A role for fibroblasts in corneal fibrosis . J Biol Chem 2003 ; 278 : 45629 – 45637 . Google Scholar Crossref Search ADS PubMed WorldCat 77 Hashmani K , Branch MJ, Sidney LE et al. Characterisation of corneal stromal stem cells with the potential for epithelial transdifferentiation . Stem Cell Res Ther 2013 ; 4 : 75 . Google Scholar Crossref Search ADS PubMed WorldCat 78 Wu J , Du Y, Mann MM et al. Bioengineering organized, multilamellar human corneal stromal tissue by growth factor supplementation on highly aligned synthetic substrates . Tissue Eng Part A 2013 ; 19 : 2063 – 2075 . Google Scholar Crossref Search ADS PubMed WorldCat 79 Wilson SL , Yang Y, El Haj AJ. Corneal stromal cell plasticity: In vitro regulation of cell phenotype through cell-cell interactions in a three-dimensional model . Tissue Eng Part A 2014 ; 20 : 225 – 238 . Google Scholar Crossref Search ADS PubMed WorldCat 80 Du Y , Sundarraj N, Funderburgh ML et al. Secretion and organization of a cornea-like tissue in vitro by stem cells from human corneal stroma . Invest Ophthalmol Vis Sci 2007 ; 48 : 5038 – 5045 . Google Scholar Crossref Search ADS PubMed WorldCat 81 Sosnova M , Bradl M, Forrester JV. CD34+ corneal stromal cells are bone marrow-derived and express hemopoietic stem cell markers . Stem Cells 2005 ; 23 : 507 – 515 . Google Scholar Crossref Search ADS PubMed WorldCat 82 Choong PF , Mok PL, Cheong SK et al. Mesenchymal stromal cell-like characteristics of corneal keratocytes . Cytotherapy 2007 ; 9 : 252 – 258 . Google Scholar Crossref Search ADS PubMed WorldCat 83 Li GG , Zhu YT, Xie HT et al. Mesenchymal stem cells derived from human limbal niche cells . Invest Ophthalmol Vis Sci 2012 ; 53 : 5686 – 5697 . Google Scholar Crossref Search ADS PubMed WorldCat 84 Kuroda N , Nakayama H, Miyazaki E et al. Distribution and role of CD34-positive stromal cells and myofibroblasts in human normal testicular stroma . Histol Histopathol 2004 ; 19 : 743 – 751 . Google Scholar PubMed OpenURL Placeholder Text WorldCat 85 Junquera C , Martinez-Ciriano C, Castiella T et al. Immunohistochemical and ultrastructural characteristics of interstitial cells of Cajal in the rabbit duodenum. Presence of a single cilium . J Cell Mol Med 2007 ; 11 : 776 – 787 . Google Scholar Crossref Search ADS PubMed WorldCat 86 Vanderwinden JM , Rumessen JJ, De Laet MH et al. CD34 immunoreactivity and interstitial cells of Cajal in the human and mouse gastrointestinal tract . Cell Tissue Res 2000 ; 302 : 145 – 153 . Google Scholar Crossref Search ADS PubMed WorldCat 87 Bucala R . Circulating fibrocytes: Cellular basis for NSF . J Am Coll Radiol 2008 ; 5 : 36 – 39 . Google Scholar Crossref Search ADS PubMed WorldCat 88 Hsu YC , Pasolli HA, Fuchs E. Dynamics between stem cells, niche, and progeny in the hair follicle . Cell 2011 ; 144 : 92 – 105 . Google Scholar Crossref Search ADS PubMed WorldCat 89 Poblet E , Jimenez F, Godinez JM et al. The immunohistochemical expression of CD34 in human hair follicles: A comparative study with the bulge marker CK15 . Clin Exp Dermatol 2006 ; 31 : 807 – 812 . Google Scholar Crossref Search ADS PubMed WorldCat 90 Ohyama M , Terunuma A, Tock CL et al. Characterization and isolation of stem cell-enriched human hair follicle bulge cells . J Clin Invest 2006 ; 116 : 249 – 260 . Google Scholar Crossref Search ADS PubMed WorldCat 91 Oh JH , Mohebi P, Farkas DL et al. Towards expansion of human hair follicle stem cells in vitro . Cell Prolif 2011 ; 44 : 244 – 253 . Google Scholar Crossref Search ADS PubMed WorldCat 92 Jiang S , Zhao L, Purandare B et al. Differential expression of stem cell markers in human follicular bulge and interfollicular epidermal compartments . Histochem Cell Biol 2010 ; 133 : 455 – 465 . Google Scholar Crossref Search ADS PubMed WorldCat 93 Amoh Y , Li L, Katsuoka K et al. Multipotent nestin-positive, keratin-negative hair-follicle bulge stem cells can form neurons . Proc Natl Acad Sci USA 2005 ; 102 : 5530 – 5534 . Google Scholar Crossref Search ADS PubMed WorldCat 94 Banh A , Xiao N, Cao H et al. A novel aldehyde dehydrogenase-3 activator leads to adult salivary stem cell enrichment in vivo . Clin Cancer Res 2011 ; 17 : 7265 – 7272 . Google Scholar Crossref Search ADS PubMed WorldCat 95 Pringle S , Van Os R, Coppes RP. Concise review: Adult salivary gland stem cells and a potential therapy for xerostomia . Stem Cells 2012 ; 31 : 613 – 619 . Google Scholar Crossref Search ADS WorldCat 96 Perrella G , Scott CA, Spelat R et al. Cultured hyman keratocytes from the limbus and cornea both express epithelial cytokeratin 3: Possible mesenchymal-epithelial transition . Int J Ophthalmic Pathol 2012 ; 1 : 1 – 7 . Google Scholar Crossref Search ADS WorldCat 97 Lemmer ER , Shepard EG, Blakolmer K et al. Isolation from human fetal liver of cells co-expressing CD34 haematopoietic stem cell and CAM 5.2 pancytokeratin markers . J Hepatol 1998 ; 29 : 450 – 454 . Google Scholar Crossref Search ADS PubMed WorldCat 98 Hristov M , Weber C. Endothelial progenitor cells in vascular repair and remodeling . Pharmacol Res 2008 ; 58 : 148 – 151 . Google Scholar Crossref Search ADS PubMed WorldCat 99 Brenes RA , Bear M, Jadlowiec C et al. Cell-based interventions for therapeutic angiogenesis: Review of potential cell sources . Vascular 2012 ; 20 : 360 – 368 . Google Scholar Crossref Search ADS PubMed WorldCat 100 Mackie AR , Losordo DW. CD34-positive stem cells: In the treatment of heart and vascular disease in human beings . Tex Heart Inst J 2011 ; 38 : 474 – 485 . Google Scholar PubMed OpenURL Placeholder Text WorldCat 101 Siemerink MJ , Klaassen I, Vogels IM et al. CD34 marks angiogenic tip cells in human vascular endothelial cell cultures . Angiogenesis 2012 ; 15 : 151 – 163 . Google Scholar Crossref Search ADS PubMed WorldCat 102 Schlingemann RO , Rietveld FJ, de Waal RM et al. Leukocyte antigen CD34 is expressed by a subset of cultured endothelial cells and on endothelial abluminal microprocesses in the tumor stroma . Lab Invest 1990 ; 62 : 690 – 696 . Google Scholar PubMed OpenURL Placeholder Text WorldCat 103 Lanza F , Healy L, Sutherland DR. Structural and functional features of the CD34 antigen: An update . J Biol Regul Homeost Agents 2001 ; 15 : 1 – 13 . Google Scholar PubMed OpenURL Placeholder Text WorldCat © 2014 The Authors. STEM CELLS Published by Wiley Periodicals, Inc. on behalf of AlphaMed Press This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by/4.0/), which permits non-commercial reuse, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
TI - Concise Review: Evidence for CD34 as a Common Marker for Diverse Progenitors
JF - Stem Cells
DO - 10.1002/stem.1661
DA - 2014-06-01
UR - https://www.deepdyve.com/lp/oxford-university-press/concise-review-evidence-for-cd34-as-a-common-marker-for-diverse-3GuGvTyO4B
SP - 1380
EP - 1389
VL - 32
IS - 6
DP - DeepDyve
ER -