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Rapid Communication| Volume 12, ISSUE 3, P332-337, 2010

Human cardiac tissue induces transdifferentiation of adult stem cells towards cardiomyocytes

      Abstract

      Background aims

      The goal was to induce the transdifferentiation (or conversion) of human adipose-derived stem cells to cardiomyocytes using an intracellular extract obtained from adult human heart tissue.

      Methods

      Human adult stem cells from lipoaspirates were transiently permeabilized, exposed to human atrial extracts and allowed to recover in culture.

      Results

      After 21 days, the cells acquired a cardiomyocyte phenotype, as demonstrated by morphologic changes (appearance of binucleate, striated cells and branching fibers), immunofluorescence detection of cardiac-specific markers (connexin-43, sarcomeric α-actinin, cardiac troponin I and T, and desmin) and the presence of cardiomyocyte-related genes analyzed by reverse transcription–polymerase chain reaction (cardiac myosin light chain 1, α-cardiac actin, cardiac troponin T and cardiac β-myosin).

      Conclusions

      We have demonstrated for the first time that adult cardiomyocytes obtained from human donors retain the capacity to induce cardiomyocyte differentiation of mesenchymal stromal cells. The use of autologous extracts for reprogramming adult stem cells may have potential therapeutic implications for treating heart disease.

      Key Words

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      References

        • Laflamme M.A.
        • Murry C.E.
        Regenerating the heart.
        Nat Biotechnol. 2005; 23: 845-856
        • Urbanek K.
        • Cesselli D.
        • Rota M.
        • Nascimbene A.
        • de Angelis A.
        • Hosoda T.
        • et al.
        Stem cell niches in the adult mouse heart.
        Proc Natl Acad Sci USA. 2006; 103: 9226-9231
        • Guan K.
        • Hasenfuss G.
        Do stem cells in the heart truly differentiate into cardiomyocytes?.
        J Mol Cell Cardiol. 2007; 43: 377-387
        • Romanov Y.A.
        • Darevskaya A.N.
        • Merzlikina N.V.
        • Buravkova L.B.
        Mesenchymal stem cells from human bone marrow and adipose tissue: isolation, characterization, and differentiation potentialities.
        Bull Exp Biol Med. 2005; 140: 138-143
        • Håkelien A.M.
        • Landsverk H.B.
        • Robl J.M.
        • Skålhegg B.S.
        • Collas P.
        Reprogramming fibroblasts to express T-cell functions using cell extracts.
        Nat. Biotechnol. 2002; 20: 460-466
        • Jin X.B.
        • Sun Y.S.
        • Zhang K.
        • Wang J.
        • Ju X.D.
        • Lou S.Q.
        Neocartilage formation from predifferentiated human adipose derived stem cells in vivo.
        Acta Pharmacol Sin. 2007; 28: 663-671
        • Gaustad K.G.
        • Boquest A.C.
        • Anderson B.E.
        • Gerdes A.M.
        • Collas P.
        Differentiation of human adipose tissue stem cells using extracts of rat cardiomyocytes.
        Biochem Biophys Res Commun. 2004; 314: 420-427
        • Gimble J.M.
        • Katz A.J.
        • Bunnell B.A.
        Adipose-derived stem cells for regenerative medicine.
        Circ Res. 2007; 100: 1249-1260
        • Makino S.
        • Fukuda K.
        • Miyoshi S.
        • Konishi F.
        • Kodama H.
        • Pan J.
        • et al.
        Cardiomyocytes can be generated from marrow stromal cells in vitro.
        J Clin Invest. 1999; 103: 697-705
        • Moore J.C.
        • Tsang S.Y.
        • Rushing S.N.
        • Lin D.
        • Tse H.F.
        • Chan C.W.
        • et al.
        Functional consequences of overexpressing the gap junction Cx43 in the cardiogenic potential of pluripotent human embryonic stem cells.
        Biochem Biophys Res Commun. 2008; 377: 46-51
        • Höllrigl A.
        • Hofner M.
        • Stary M.
        • Weitzer G.
        Differentiation of cardiomyocytes requires functional serine residues within the amino-terminal domain of desmin.
        Differentiation. 2007; 75: 616-626
        • Bai X.
        • Pinkernell K.
        • Song Y.H.
        • Nabzdyk C.
        • Reiser J.
        • Alt E.
        Genetically selected stem cells from human adipose tissue express cardiac markers.
        Biochem Biophys Res Commun. 2007; 353: 665-671
        • Chen Z.
        • Huang W.
        • Dahme T.
        • Rottbauer W.
        • Ackerman M.J.
        • Xu X.
        Depletion of zebrafish essential and regulatory myosin light chains reduces cardiac function through distinct mechanisms.
        Cardiovasc Res. 2008; 79: 97-108
        • Rangappa S.
        • Entwistle J.W.
        • Wechsler A.S.
        • Kresh J.Y.
        Cardiomyocyte-mediated contact programs human mesenchymal stem cells to express cardiogenic phenotype.
        J Thorac Cardiovasc Surg. 2003; 126: 124-132
        • Miguel J.
        • Erices A.
        Mesenchymal stem cells and the treatment of cardiac disease.
        Exp Biol Med. 2006; 231: 39-49
        • Schimrosczyk K.
        • Song Y.H.
        • Vykoukal J.
        • Vykoukal D.
        • Bai X.
        • Krohn A.
        • et al.
        Liposome-mediated transfection with extract from neonatal rat cardiomyocytes induces transdifferentiation of human adipose-derived stem cells into cardiomyocytes.
        Scand J Clin Lab Invest. 2008; 68: 464-472
        • Koninckx R.
        • Hensen K.
        • Daniëls A.
        • Moreels M.
        • Lambrichts I.
        • Jongen H.
        • et al.
        Human bone marrow stem cells co-cultured with neonatal rat cardiomyocytes display limited cardiomyogenic plasticity.
        Cytotherapy. 2009; 11: 778-792
        • Takeuchi J.K.
        • Bruneau B.G.
        Directed transdifferentiation of mouse mesoderm to heart tissue by defined factors.
        Nature. 2009; 459: 654-655