Human embryonic stem cell-derived CD34+ cells function as MSC progenitor cells

Kopher, Ross A.; Penchev, Vesselin R.; Islam, Mohammad Saiful; Hill, Katherine; Khosla, Sundeep; Kaufman, Dan S.

doi:10.1016/j.bone.2010.06.020

Cited by 57 publications

(66 citation statements)

References 54 publications

(67 reference statements)

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“…In contrast, H1-MSCs, WA1-MSCs, and BM-MSCs express MSC surface markers yet H1-MSCs andWA1-MSCs express a lower level of CD106 compared to BM-MSCs. Similar findings demonstrating that ESC-MSCs express low levels of MSC markers, CD105 and CD106, have been reported (Hwang et al 2008a, b; Kopher et al 2010). Additionally, CD106 has been shown to be associated with the multi-lineage differentiation potential of adult tissue-derived MSCs, as the expression level of CD106 decreases with progression of differentiation (Liu et al 2008).…”

Section: Discussionsupporting

confidence: 89%

Characterization and evaluation of mesenchymal stem cells derived from human embryonic stem cells and bone marrow

Brown

Squire

2014

Cell Tissue Res

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Embryonic stem cells (ESCs) and mesenchymal stem cells (MSCs) have been studied for years as primary cell sources for regenerative biology and medicine. MSCs have been derived from cell and tissue sources, such as bone marrow (BM), and more recently from ESCs. This study investigated MSCs derived from BM, H1- and H9-ESC lines in terms of morphology, surface marker and growth factor receptor expression, proliferative capability, modulation of immune cell growth and multipotency, in order to evaluate ESC-MSCs as a cell source for potential regenerative applications. The results showed that ESC-MSCs exhibited spindle-shaped morphology similar to BM-MSCs but of various sizes, and flow cytometric immunophenotyping revealed expression of characteristic MSC surface markers on all tested cell lines except H9-derived MSCs. Differences in growth factor receptor expression were also shown between cell lines. In addition, ESC-MSCs showed greater capabilities for cell proliferation, and suppression of leukocyte growth compared to BM-MSCs. Using standard protocols, induction of ESC-MSC differentiation along the adipogenic, osteogenic, or chondrogenic lineages was less effective compared to that of BM-MSCs. By adding bone morphogenetic protein 7 (BMP7) into transforming growth factor beta 1 (TGFβ1)-supplemented induction medium, chondrogenesis of ESC-MSCs was significantly enhanced. Our findings suggest that ESC-MSCs and BM-MSCs show differences in their surface marker profiles and the capacities of proliferation, immunomodulation, and most importantly multi-lineage differentiation. Using modified chondrogenic medium with BMP7 and TGFβ1, H1-MSCs can be effectively induced as BM-MSCs for chondrogenesis.

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Section: Discussionsupporting

confidence: 89%

Characterization and evaluation of mesenchymal stem cells derived from human embryonic stem cells and bone marrow

Brown

Squire

2014

Cell Tissue Res

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“…Recently, Kopher et al demonstrated that hESC-derived CD34 ϩ endothelial precursors have phenotypic and functional features similar to MSCs. 38 Therefore, Ang1-EC-ESCs may contain MSC components. When Ang1-ECESCs were plated on a 0.1% gelatin-coated dish in EGM-2 medium, they showed a typical cobblestone-like appearance as early as 6 hours from the start of incubation ( Figure 6A).…”

Section: Ang1-induced Ecs Have a Neovasculogenic Potential In Vitro Amentioning

confidence: 99%

Angiopoietin-1 promotes endothelial differentiation from embryonic stem cells and induced pluripotent stem cells

Joo

Kim

Park

et al. 2011

Blood

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Angiopoietin-1 (Ang1) plays a crucial role in vascular and hematopoietic development, mainly through its cognate receptor Tie2. However, little is known about the precise role of Ang1 in embryonic stem cell (ESC) differentiation. In the present study, we used COMP-Ang1 (a soluble and potent variant of Ang1) to explore the effect of Ang1 on endothelial and hematopoietic differentiation of mouse ESCs in an OP9 coculture system and found that Ang1 promoted endothelial cell (EC) differentiation from Flk-1 ؉ mesodermal precursors. This effect mainly occurred through Tie2 signaling and was altered in the presence of soluble Tie2-Fc. We accounted for this Ang1-induced expansion of ECs as enhanced proliferation and survival. Ang1 also had an effect on CD41 ؉ cells, transient precursors that can differentiate into both endothelial and hematopoietic lineages. IntroductionEmbryonic stem cells (ESCs) have been used frequently not only for research in the field of developmental biology, but also in cell-based regenerative medicine. 1 Many scientists in the field of vascular biology have studied the endothelial cell (EC) differentiation of ESCs in an attempt to develop treatments for the associated pathologies, and therefore our knowledge of EC differentiation has significantly expanded. 2,3 However, the pluripotency of ESCs capable of generating various cell types and the overwhelming complexity of the multiple signaling pathways involved in the process of differentiation make it extremely challenging to control EC differentiation in a precise and efficient manner. Our knowledge of ESC-EC differentiation still remains far from satisfactory, and the possibility of successfully applying stem cells in vascular regenerative medicine remains merely optimistic.Several recent studies have provided evidence supporting the presence of an intimate linkage between ECs and hematopoietic cells (HCs) during early embryonic development. 4,5 It has been suggested that both the endothelial and hematopoietic lineages arise from a common progenitor, the hemangioblasts, which express Flk-1 during the early stage of differentiation. 6-8 Moreover, several studies have suggested that the Flk-1 ϩ cells at this stage are actually mesodermal precursor cells (MPCs), based on the fact that they can give rise to not only ECs and HSCs but also to vascular smooth muscle cells (VSMCs) and even cardiomyocytes. 9,10 Recent studies have also demonstrated that some HSCs are derived from a subset of ECs called the hemogenic endothelium during the differentiation from ESCs. [11][12][13] Other studies revealed that the initial definitive hematopoietic cells could originate from hemogenic endothelium that resides in the aorta during early embryonic development. 14-16 However, the underlying link between ECs and HSCs still remains obscure and is the subject of controversy.During the early stages of life, various growth factors influence endothelial and hematopoietic development. Among them, Ang1, a cognate ligand for the Tie2 receptor, is one of the key molecules ...

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“…+ cells as precursors of human (Kopher et al, 2010) and murine (Kaiser et al, 2007) MSC. Interestingly, the CD34 expression in long-term MSC culture was observed , in addition to report demonstrating higher angiogenic potential of CD34 + subpopulation of MSC (Copland et al, 2008), what is altogether consistent with our study.…”

Section: Cd34mentioning

confidence: 99%

CD45-CD14+CD34+ Murine Bone Marrow Low-Adherent Mesenchymal Primitive Cells Preserve Multilineage Differentiation Potential in Long-Term In Vitro Culture

Szade

Zuba‐Surma

Rutkowski

et al. 2011

Molecules and Cells

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Bone marrow-derived cells have been postulated as a source of multipotent mesenchymal stem cells (MSC). However, the whole fraction of MSC remains heterogeneous and the expansion of primitive subset of these cells is still not well established. Here, we optimized the protocol for propagating the low-adherent subfraction of MSC which results in long-term expansion of population characterized by CD45+ phenotype along with expression of common MSC markers. We established that the expanded MSC are capable of differentiating into endothelial cells highly expressing angiogenic markers and exhibiting functional properties of endothelium. Moreover, we found these cells to be multipotent and capable of giving rise into cells from neuronal lineages. Interestingly, the expanded MSC form characteristic cellular spheres in vitro indicating primitive features of these cells. In sum, we isolated the novel multipotent subpopulation of CD45+ bone marrow-derived cells that could be maintained in long-term culture without losing this potential.

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Human embryonic stem cell-derived CD34+ cells function as MSC progenitor cells

Cited by 57 publications

References 54 publications

Characterization and evaluation of mesenchymal stem cells derived from human embryonic stem cells and bone marrow

Characterization and evaluation of mesenchymal stem cells derived from human embryonic stem cells and bone marrow

Angiopoietin-1 promotes endothelial differentiation from embryonic stem cells and induced pluripotent stem cells

CD45-CD14+CD34+ Murine Bone Marrow Low-Adherent Mesenchymal Primitive Cells Preserve Multilineage Differentiation Potential in Long-Term In Vitro Culture

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