A purified population of multipotent cardiovascular progenitors derived from primate pluripotent stem cells engrafts in postmyocardial infarcted nonhuman primates
Author
Blin, Guillaume
Nury, David
Stefanovic, Sonia
Neri, Tui
Guillevic, Oriane
Brinon, Benjamin
Bellamy, Valérie
Rücker-Martin, Catherine
Barbry, Pascal
Bel, Alain
Bruneval, Patrick
Pouly, Julia
Mitalipov, Shoukhrat
Gouadon, Elodie
Binder, Patrice
Hagège, Albert
Desnos, Michel
Renaud, Jean-François
Menasché, Philippe
Pucéat, Michel
Note: Order does not necessarily reflect citation order of authors.
Published Version
https://doi.org/10.1172/JCI40120Metadata
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Blin, Guillaume, David Nury, Sonia Stefanovic, Tui Neri, Oriane Guillevic, Benjamin Brinon, Valérie Bellamy, et al. 2010. “A Purified Population of Multipotent Cardiovascular Progenitors Derived from Primate Pluripotent Stem Cells Engrafts in Postmyocardial Infarcted Nonhuman Primates.” J. Clin. Invest. 120 (4) (April 1): 1125–1139. doi:10.1172/jci40120.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.Other Sources
http://www.ncbi.nlm.nih.gov/pubmed/20335662Terms of Use
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http://nrs.harvard.edu/urn-3:HUL.InstRepos:14068404
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