Flk1 and VE-Cadherin Endothelial Cells Derived from iPSCs Recapitulates Vascular Development during Differentiation and Display Similar Angiogenic Potential as ESC-Derived CellsReportar como inadecuado




Flk1 and VE-Cadherin Endothelial Cells Derived from iPSCs Recapitulates Vascular Development during Differentiation and Display Similar Angiogenic Potential as ESC-Derived Cells - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

Rationale

Induced pluripotent stem iPS cells have emerged as a source of potentially unlimited supply of autologous endothelial cells ECs for vascularization. However, the regenerative function of these cells relative to adult ECs and ECs derived from embryonic stem ES cells is unknown. The objective was to define the differentiation characteristics and vascularization potential of Fetal liver kinase Flk1+ and Vascular Endothelial VE-cadherin+ ECs derived identically from mouse mES and miPS cells.

Methods and Results

Naive mES and miPS cells cultured in type IV collagen IV Col in defined media for 5 days induced the formation of adherent cell populations, which demonstrated similar expression of Flk1 and VE-cadherin and the emergence of EC progenies. FACS purification resulted in 100% Flk1+ VE-cadherin+ cells from both mES and miPS cells. Emergence of Flk1+VE-cadherin+ cells entailed expression of the vascular developmental transcription factor Er71, which bound identically to Flk1, VE-cadherin, and CD31 promoters in both populations. Immunostaining with anti-VE-cadherin and anti-CD31 antibodies and microscopy demonstrated the endothelial nature of these cells. Each cell population unlike mature ECs organized into well-developed vascular structures in vitro and incorporated into CD31+ neovessels in matrigel plugs implanted in nude mice in vivo.

Conclusion

Thus, iPS cell-derived Flk1+VE-cadherin+ cells expressing the Er71 are as angiogenic as mES cell-derived cells and incorporate into CD31+ neovessels. Their vessel forming capacity highlights the potential of autologous iPS cells-derived EC progeny for therapeutic angiogenesis.



Autor: Erin E. Kohler, Kishore K. Wary , Fei Li, Ishita Chatterjee, Norifumi Urao, Peter T. Toth, Masuko Ushio-Fukai, Jalees Rehman, Cha

Fuente: http://plos.srce.hr/



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