TY - JOUR
T1 - A purified population of multipotent cardiovascular progenitors derived from primate pluripotent stem cells engrafts in postmyocardial infarcted nonhuman primates
AU - Blin, Guillaume
AU - Nury, David
AU - Stefanovic, Sonia
AU - Neri, Tui
AU - Guillevic, Oriane
AU - Brinon, Benjamin
AU - Bellamy, Valérie
AU - Rücker-Martin, Catherine
AU - Barbry, Pascal
AU - Bel, Alain
AU - Bruneval, Patrick
AU - Cowan, Chad
AU - Pouly, Julia
AU - Mitalipov, Shoukhrat
AU - Gouadon, Elodie
AU - Binder, Patrice
AU - Hagège, Albert
AU - Desnos, Michel
AU - Renaud, Jean François
AU - Menasché, Philippe
AU - Pucéat, Michel
PY - 2010/4/1
Y1 - 2010/4/1
N2 - 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.
AB - 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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U2 - 10.1172/JCI40120
DO - 10.1172/JCI40120
M3 - Article
C2 - 20335662
AN - SCOPUS:77951181560
SN - 0021-9738
VL - 120
SP - 1125
EP - 1139
JO - Journal of Clinical Investigation
JF - Journal of Clinical Investigation
IS - 4
ER -