Identification and Characterization of a KDR-positive Mesoderm Population Derived from Human Embryonic Stem Cells Post BMP4 Treatment
2011
Kim, J.M., Graduate School of Life Science, CHA Stem Cell Institute, CHA University, College of Medicine, Seoul, Republic of Korea | Son, O.J., Graduate School of Life Science, CHA Stem Cell Institute, CHA University, College of Medicine, Seoul, Republic of Korea | Cho, Y.J., Graduate School of Life Science, CHA Stem Cell Institute, CHA University, College of Medicine, Seoul, Republic of Korea | Lee, J.H., CHA Biotech and Diostech Co., Ltd., Seoul, Republic of Korea | Chung, H.M., Graduate School of Life Science, CHA Stem Cell Institute, CHA University, College of Medicine, Seoul, Republic of Korea
The functional cardiovascular system is comprised of distinct mesoderm-derived lineages including endothelial cells, vascular smooth muscle cells and other mesenchymal cells. Recent studies in the human embryonic stem cell differentiation model have provided evidence indicating that these cell lineages are developed from the common progenitors such as hemangioblasts and cardiovascular progenitor cells. Also, the studies have suggested that these progenitors have a common primordial progenitor, which expresses KDR (human Flk-1, also known as VEGFR2, CD309). We demonstrate here that sustained activation of BMP4 (bone morphogenetic protein 4) in hESC line, CHA15 hESC results in KDR+ mesoderm specific differentiation. To determine whether the KDR+ population derived from hESCs enhances potential to differentiate along multipotential mesodermal lineages than undifferentiated hESCs, we analyzed the development of the mesodermal cell types in human embryonic stem cell differentiation cultures. In embryoid body (EB) differentiation culture conditions, we identified an increased expression of KDR+ population from BMP4-stimulated hESC-derived EBs. After induction with additional growth factors, the KDR+ population sorted from hESCs-derived EBs displays mesenchymal, endothelial and vascular smooth muscle potential in matrix-coated monolayer culture systems. The populations plated in monolayer cultures expressed increased levels of related markers and exhibit a stable/homologous phenotype in culture terms. In conclusion, we demonstrate that the KDR+ population is stably isolated from CHA15 hESC-derived EBs using BMP4 and growth factors, and sorted KDR+ population can be utilized to generate multipotential mesodermal progenitors in vitro, which can be further differentiated into cardiovascular specific cells.
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