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, Oriane Guillevic, Benjamin Brinon, Valérie Bellamy, Catherine Rücker-Martin, Pascal Barbry, Alain Bel, Patrick Bruneval, Chad Cowan, Julia Pouly, Shoukhrat Mitalipov, Elodie Gouadon, Patrice Binder, Albert Hagège, Michel Desnos, Jean François Renaud, Philippe MenaschéMichel Pucéat

    Research output: Contribution to journalArticle

    231 Citations (Scopus)

    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.

    Original languageEnglish (US)
    Pages (from-to)1125-1139
    Number of pages15
    JournalJournal of Clinical Investigation
    Volume120
    Issue number4
    DOIs
    StatePublished - Apr 1 2010

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    CD15 Antigens
    Pluripotent Stem Cells
    Primates
    Population
    Cell- and Tissue-Based Therapy
    Cicatrix
    Heart Diseases
    Forensic Anthropology
    Adult Stem Cells
    Regenerative Medicine
    Teratoma
    Mesoderm
    Embryonic Stem Cells
    Cardiac Myocytes
    Bone Marrow Cells
    Muscle Cells
    Smooth Muscle Myocytes
    Regeneration
    Myocardium
    Skeletal Muscle

    ASJC Scopus subject areas

    • Medicine(all)

    Cite this

    A purified population of multipotent cardiovascular progenitors derived from primate pluripotent stem cells engrafts in postmyocardial infarcted nonhuman primates. / Blin, Guillaume; Nury, David; Stefanovic, Sonia; Neri, Tui; Guillevic, Oriane; Brinon, Benjamin; Bellamy, Valérie; Rücker-Martin, Catherine; Barbry, Pascal; Bel, Alain; Bruneval, Patrick; Cowan, Chad; Pouly, Julia; Mitalipov, Shoukhrat; Gouadon, Elodie; Binder, Patrice; Hagège, Albert; Desnos, Michel; Renaud, Jean François; Menasché, Philippe; Pucéat, Michel.

    In: Journal of Clinical Investigation, Vol. 120, No. 4, 01.04.2010, p. 1125-1139.

    Research output: Contribution to journalArticle

    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 2010, 'A purified population of multipotent cardiovascular progenitors derived from primate pluripotent stem cells engrafts in postmyocardial infarcted nonhuman primates', Journal of Clinical Investigation, vol. 120, no. 4, pp. 1125-1139. https://doi.org/10.1172/JCI40120
    Blin, Guillaume ; Nury, David ; Stefanovic, Sonia ; Neri, Tui ; Guillevic, Oriane ; Brinon, Benjamin ; Bellamy, Valérie ; Rücker-Martin, Catherine ; Barbry, Pascal ; Bel, Alain ; Bruneval, Patrick ; Cowan, Chad ; Pouly, Julia ; Mitalipov, Shoukhrat ; Gouadon, Elodie ; Binder, Patrice ; Hagège, Albert ; Desnos, Michel ; Renaud, Jean François ; Menasché, Philippe ; Pucéat, Michel. / A purified population of multipotent cardiovascular progenitors derived from primate pluripotent stem cells engrafts in postmyocardial infarcted nonhuman primates. In: Journal of Clinical Investigation. 2010 ; Vol. 120, No. 4. pp. 1125-1139.
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    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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    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

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