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

Guillaume Blin; David Nury; Sonia Stefanovic; Tui Neri; Orianne Guillevic; Benjamin Brinon; Valérie Bellamy; Catherine Rücker-Martin; Pascal Barbry; Alain Bel; Lionel Bonnevie; Patrick Bruneval; Chad Cowan; Julia Pouly; Shoukhrat Mitalipov; Elodie Gouadon; Patrice Binder; Albert Hagège; Michel Desnos; Philippe Menasché; Jean-François Renaud; Michel Puceat

doi:10.1172/JCI40120

Journal articles

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

Guillaume Blin ¹ David Nury ¹ Sonia Stefanovic ¹ Tui Neri ¹ Orianne Guillevic ¹ Benjamin Brinon ^{1, 2} Valérie Bellamy ² Catherine Rücker-Martin ³ Pascal Barbry ⁴ Alain Bel ⁵ Lionel Bonnevie ⁶ Patrick Bruneval ⁷ Chad Cowan ⁸ Julia Pouly ⁵ Shoukhrat Mitalipov ⁹ Elodie Gouadon ³ Patrice Binder ¹⁰ Albert Hagège ^{2, 11} Michel Desnos ^{2, 11} Philippe Menasché ^{2, 5, *} Jean-François Renaud ³ Michel Puceat ^{1, 12, *}

* Corresponding author

1 I-STEM - Institut des cellules souches pour le traitement et l'étude des maladies monogéniques

2 UMR_S 633 - Therapie Cellulaire en Pathologie Cardio-Vasculaire

3 RTFSPP - Remodelage tissulaire et fonctionnel : signalisation et physio-pathologie

4 IPMC - Institut de pharmacologie moléculaire et cellulaire

5 Service de chirurgie cardiaque et vasculaire [CHU HEGP]

6 Service de cardiologie

7 Service d'anatomo-pathologie [CHU HEGP]

8 Stowers Medical Institute

9 Division of Reproductive Sciences

10 IMASSA - Institut de Médecine Aérospatiale du Service de Santé des Armées

11 Service de cardiologie [CHU HEGP]

12 Equipe avenir HUMAN EMBRYONIC STEM CELLS AS A MODEL TO DELINEATE THE EARLY CARDIAC TRANSCRIPTIONAL NETWORKS: TOWARD A BETTER UNDERSTANDING OF CARDIAC CONGENITAL AND GENETIC DISEASES.

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.

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Journal articles

Domain :

Life Sciences [q-bio] / Human health and pathology / Cardiology and cardiovascular system

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

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

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