Abstract 14897: Robust Reprogramming Of human Placenta derived Mesenchymal Stem Cells Into Spontaneously Contractile Cardiomyocytes
Background. Human placenta-derived mesenchymal stem cells (hPMSCs) represent a unique population of stem cells. They demonstrate partial pluripotency, immunomodulatory properties, and c-kit (CD117) cardiac progenitor cell surface marker. In this study, c-kit (+) subpopulation of hPMSCs was selected to generate iPSCs.
Hypothesis. We hypothesized that these hPMSC-derived iPSCs (MiPSCs) will exhibit high cardiac differentiation efficiency.
Methods and Results. A single polycistronic lentivirus was introduced into c-kit (+) hPMSCs to generate MiPSCs. Immunohistology revealed that the immunomodulatory and pre-cardiac mesodermal properties were retained in the MiPSCs (Figure 1). To investigate the ability of c-kit (+) MiPSCs to generate spontaneously contractile cardiomyocytes, MiPSCs were cultured on a Matrigel matrix in a serum-free RMIP1640/B27 medium, supplemented by sequential addition of Activin A and BMP4. Contractile areas were observed as early as day 4 after induction with Activin A and BMP4(Figure 1).
Conclusion. MiPSCs may represent an unlimited source of universal cardiac progenitor cells for clinical application. Multiple approaches have been described for directed and efficient differentiation of human pluripotent stem cells. However,there are inconsistencies in differentiation efficiency of hESC and iPSC lines. Our data revealed that the MiPSCs derived from c-kit (+) hPMSCs retained the cardiac progenitor and immunomodulatory properties and readily demonstrated spontaneous contractility in a very short period of time. These unique characteristics of MiPSCs will enable a robust and safe method to generate universal, off-the-shelf supply of cardiac progenitor cells. This study validates a cell-specific approach to translate novel stem cell biology for restoration of the injured myocardium.
- Stem/progenitor cells
- Regenerative medicine stem cells
- Heart disease
- Immunosuppressive therapy
- © 2011 by American Heart Association, Inc.