J Clin Invest. 2010 Apr 1;120(4):1125-39. doi: 10.1172/JCI40120. Epub 2010 Mar 24.

A purified population of multipotent cardiovascular progenitors derived from primate pluripotent stem cells engrafts in postmyocardial infarcted nonhuman primates.

Blin G, Nury D, Stefanovic S, Neri T, Guillevic O, Brinon B, Bellamy V, Rücker-Martin C, Barbry P, Bel A, Bruneval P, Cowan C, Pouly J, Mitalipov S, Gouadon E, Binder P, Hagège A, Desnos M, Renaud JF, Menasché P, Pucéat M.

INSERM U633, Avenir Program, Embryonic Stem Cells and Cardiogenesis, Evry, France. University Montpellier II, France. INSERM U633,University Paris Descartes, France. CNRS-UMR 8162, Université Paris-Sud, and Hôpital Marie Lannelongue, Le Plessis Robinson, France. CNRS, University of Nice Sophia Antipolis, Institut de Pharmacologie Moléculaire et Cellulaire, Nice, France. Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Européen Georges-Pompidou, Department of Cardiovascular Surgery, Paris, France. AP-HP, Hôpital Européen Georges-Pompidou, Department of Pathology, and INSERM U970, Paris, France. Stowers Medical Institute, Center for Regenerative Medicine and Technology, Cardiovascular Research Center, Boston, Massachusetts. Division of Reproductive Sciences, Oregon National Primate Research Center, Beaverton. Institut de Médecine Aérospatiale du Service de Santé des Armées (IMASSA), Brétigny sur Orge, France. Department of Cardiology, AP-HP, Hôpital Européen Georges-Pompidou.

Abstract

Cell therapy holds promise for tissue regeneration, including in individuals with advanced heart failure. However, treatment of heart disease with bone marrow cells and skeletal muscle progenitors has had only marginal positive benefits in clinical trials, perhaps because adult stem cells have limited plasticity. The identification, among human pluripotent stem cells, of early cardiovascular cell progenitors required for the development of the first cardiac lineage would shed light on human cardiogenesis and might pave the way for cell therapy for cardiac degenerative diseases. Here, we report the isolation of an early population of cardiovascular progenitors, characterized by expression of OCT4, stage-specific embryonic antigen 1 (SSEA-1), and mesoderm posterior 1 (MESP1), derived from human pluripotent stem cells treated with the cardiogenic morphogen BMP2. This progenitor population was multipotential and able to generate cardiomyocytes as well as smooth muscle and endothelial cells. When transplanted into the infarcted myocardium of immunosuppressed nonhuman primates, an SSEA-1+ progenitor population derived from Rhesus embryonic stem cells differentiated into ventricular myocytes and reconstituted 20% of the scar tissue. Notably, primates transplanted with an unpurified population of cardiac-committed cells, which included SSEA-1- cells, developed teratomas in the scar tissue, whereas those transplanted with purified SSEA-1+ cells did not. We therefore believe that the SSEA-1+ progenitors that we have described here have the potential to be used in cardiac regenerative medicine.

Comment in J Clin Invest. 2010 Apr 1;120(4):1034-6.

PMID:20335662  PMCID: PMC2846046