Composite cell sheets: A further step toward safe and effective myocardial regeneration by cardiac progenitors derived from embryonic stem cells

Academic Article

Abstract

  • Background-: The safety and efficacy of myocardial regeneration using embryonic stem cells are limited by the risk of teratoma and the high rate of cell death. Methods and results-: To address these issues, we developed a composite construct made of a sheet of adipose tissue-derived stroma cells and embryonic stem cell-derived cardiac progenitors. Ten Rhesus monkeys underwent a transient coronary artery occlusion followed, 2 weeks later, by the open-chest delivery of the composite cell sheet over the infarcted area or a sham operation. The sheet was made of adipose tissue-derived stroma cells grown from a biopsy of autologous adipose tissue and cultured onto temperature-responsive dishes. Allogeneic Rhesus embryonic stem cells were committed to a cardiac lineage and immunomagnetically sorted to yield SSEA-1+ cardiac progenitors, which were then deposited onto the cell sheet. Cyclosporine was given for 2 months until the animals were euthanized. Preimplantation studies showed that the SSEA-1+ progenitors expressed cardiac markers and had lost pluripotency. After 2 months, there was no teratoma in any of the 5 cell-treated monkeys. Analysis of >1500 histological sections showed that the SSEA-1+ cardiac progenitors had differentiated into cardiomyocytes, as evidenced by immunofluorescence and real-time polymerase chain reaction. There were also a robust engraftment of autologous adipose tissue-derived stroma cells and increased angiogenesis compared with the sham animals. Conclusions-: These data collected in a clinically relevant nonhuman primate model show that developmentally restricted SSEA-1+ cardiac progenitors appear to be safe and highlight the benefit of the epicardial delivery of a construct harboring cells with a cardiomyogenic differentiation potential and cells providing them the necessary trophic support. © 2010 American Heart Association, Inc.
  • Published In

  • Circulation  Journal
  • Digital Object Identifier (doi)

    Author List

  • Bel A; Planat-Bernard V; Saito A; Bonnevie L; Bellamy V; Sabbah L; Bellabas L; Brinon B; Vanneaux V; Pradeau P
  • Volume

  • 122
  • Issue

  • 11 SUPPL. 1