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Regenerative Medicine

Novel 3D culture system with similarities to the human heart for studies of the cardiac stem cell niche

    Marianne Jonsson

    Department of Clinical Chemistry & Transfusion Medicine, Institute of Biomedicine, The Sahlgrenska Academy, University of Gothenburg, 413 45 Gothenburg, Sweden

    ,
    Helena B Henriksson

    Department of Clinical Chemistry & Transfusion Medicine, Institute of Biomedicine, The Sahlgrenska Academy, University of Gothenburg, 413 45 Gothenburg, Sweden

    ,
    Margret Hagman

    Department of Clinical Chemistry & Transfusion Medicine, Institute of Biomedicine, The Sahlgrenska Academy, University of Gothenburg, 413 45 Gothenburg, Sweden

    ,
    Kristina Kajic

    Department of Clinical Chemistry & Transfusion Medicine, Institute of Biomedicine, The Sahlgrenska Academy, University of Gothenburg, 413 45 Gothenburg, Sweden

    ,
    Anders Lindahl

    Department of Clinical Chemistry & Transfusion Medicine, Institute of Biomedicine, The Sahlgrenska Academy, University of Gothenburg, 413 45 Gothenburg, Sweden

    ,
    Anders Jeppsson

    Department of Molecular & Clinical Medicine, the Sahlgrenska Academy, University of Gothenburg & Department of Cardiothoracic Surgery, Sahlgrenska University Hospital, Gothenburg, Sweden

    ,
    Håkan Berggren

    Department of Molecular & Clinical Medicine, the Sahlgrenska Academy, University of Gothenburg & Department of Cardiothoracic Surgery, Sahlgrenska University Hospital, Gothenburg, Sweden

    &
    Published Online:https://doi.org/10.2217/rme.10.63

    Aims: The aim of this study was to develop a 3D culture system with similarities to the human heart, which was suitable for studies of adult cardiac stem or progenitor cells. Materials & methods: Dissociated cells from human cardiac biopsies were placed in high-density pellet cultures and cultured for up to 6 weeks. Gene and protein expressions, analyzed by quantitative real-time PCR and immunohistochemistry, and morphology were studied in early and late pellets. Results: Cells cultured in the 3D model showed similarities to human cardiac tissue. Moreover, markers for cardiac stem and progenitor cells were also detected after 6 weeks of culture, in addition to markers for signaling pathways active in stem cell niche regulation. Conclusions: The described 3D culture model could be a valuable tool when studying the influence of different compounds on proliferation and differentiation processes in cardiac stem or progenitor cells in cardiac regenerative research.

    Bibliography

    • Oberpriller JO, Oberpriller JC: Response of the adult newt ventricle to injury. J. Exp. Zool.187(2),249–253 (1974).
    • Bergmann O, Bhardwaj RD, Bernard S et al.: Evidence for cardiomyocyte renewal in humans. Science324(5923),98–102 (2009).
    • Beltrami AP, Barlucchi L, Torella D et al.: Adult cardiac stem cells are multipotent and support myocardial regeneration. Cell114(6),763–776 (2003).
    • Messina E, De Angelis L, Frati G et al.: Isolation and expansion of adult cardiac stem cells from human and murine heart. Circ. Res.95(9),911–921 (2004).
    • Tateishi K, Ashihara E, Honsho S et al.: Human cardiac stem cells exhibit mesenchymal features and are maintained through Akt/GSK-3β signaling. Biochem. Biophys. Res. Commun.352(3),635–641 (2007).
    • Urbanek K, Torella D, Sheikh F et al.: Myocardial regeneration by activation of multipotent cardiac stem cells in ischemic heart failure. Proc. Natl Acad. Sci. USA102(24),8692–8697 (2005).
    • Goumans MJ, de Boer TP, Smits AM et al.: TGF-β1 induces efficient differentiation of human cardiomyocyte progenitor cells into functional cardiomyocytes in vitro. Stem Cell Res.1(2),138–149 (2008).
    • Laugwitz KL, Moretti A, Lam J et al.: Postnatal isl1+ cardioblasts enter fully differentiated cardiomyocyte lineages. Nature433(7026),647–653 (2005).
    • Pfister O, Mouquet F, Jain M et al.: CD31- but not CD31+ cardiac side population cells exhibit functional cardiomyogenic differentiation. Circ. Res.97(1),52–61 (2005).
    • 10  Pfister O, Oikonomopoulos A, Sereti KI et al.: Role of the ATP-binding cassette transporter Abcg2 in the phenotype and function of cardiac side population cells. Circ. Res.103(8),825–835 (2008).
    • 11  Meissner K, Heydrich B, Jedlitschky G et al.: The ATP-binding cassette transporter ABCG2 (BCRP), a marker for side population stem cells, is expressed in human heart. J. Histochem. Cytochem.54(2),215–221 (2006).
    • 12  Fuchs E, Tumbar T, Guasch G: Socializing with the neighbors: stem cells and their niche. Cell116(6),769–778 (2004).
    • 13  Moore KA, Lemischka IR: Stem cells and their niches. Science311(5769),1880–1885 (2006).
    • 14  Boni A, Urbanek K, Nascimbene A et al.: Notch1 regulates the fate of cardiac progenitor cells. Proc. Natl Acad. Sci. USA105(40),15529–15534 (2008).
    • 15  Schultheiss TM, Burch JB, Lassar AB: A role for bone morphogenetic proteins in the induction of cardiac myogenesis. Genes Dev.11(4),451–462 (1997).
    • 16  Klaus A, Saga Y, Taketo MM, Tzahor E, Birchmeier W: Distinct roles of Wnt/β-catenin and BMP signaling during early cardiogenesis. Proc. Natl Acad. Sci. USA104(47),18531–18536 (2007).
    • 17  Kwon C, Arnold J, Hsiao EC et al.: Canonical Wnt signaling is a positive regulator of mammalian cardiac progenitors. Proc. Natl Acad. Sci. USA104(26),10894–10899 (2007).
    • 18  Thomas NA, Koudijs M, van Eeden FJ, Joyner AL, Yelon D: Hedgehog signaling plays a cell-autonomous role in maximizing cardiac developmental potential. Development135(22),3789–3799 (2008).
    • 19  Song X, Zhu CH, Doan C, Xie T: Germline stem cells anchored by adherens junctions in the Drosophila ovary niches. Science296(5574),1855–1857 (2002).
    • 20  Vandesompele J, De Preter K, Pattyn F et al.: Accurate normalization of real-time quantitative RT-PCR data by geometric averaging of multiple internal control genes. Genome Biol.3(7), RESEARCH0034 (2002).
    • 21  Andersen CL, Jensen JL, Orntoft TF: Normalization of real-time quantitative reverse transcription-PCR data: a model-based variance estimation approach to identify genes suited for normalization, applied to bladder and colon cancer data sets. Cancer Res.64(15),5245–5250 (2004).
    • 22  Histologisk Teknik. Moewis G (Ed.). Almqvist & Wicksell förlag AB, Stockholm, Sweden 180–181 (1978).
    • 23  Gaborit N, Le Bouter S, Szuts V et al.: Regional and tissue specific transcript signatures of ion channel genes in the nondiseased human heart. J. Physiol.582(Pt 2),675–693 (2007).
    • 24  Perez S, Royo LJ, Astudillo A et al.: Identifying the most suitable endogenous control for determining gene expression in hearts from organ donors. BMC Mol. Biol.8114 (2007).
    • 25  Synnergren J, Giesler TL, Adak S et al.: Differentiating human embryonic stem cells express a unique housekeeping gene signature. Stem Cells25(2),473–480 (2007).
    • 26  Gusterson RJ, Jazrawi E, Adcock IM, Latchman DS: The transcriptional co-activators CREB-binding protein (CBP) and p300 play a critical role in cardiac hypertrophy that is dependent on their histone acetyltransferase activity. J. Biol. Chem.278(9),6838–6847 (2003).
    • 27  Sperling S, Grimm CH, Dunkel I et al.: Identification and functional analysis of CITED2 mutations in patients with congenital heart defects. Hum. Mutat.26(6),575–582 (2005).
    • 28  Holaska JM, Rais-Bahrami S, Wilson KL: Lmo7 is an emerin-binding protein that regulates the transcription of emerin and many other muscle-relevant genes. Hum. Mol. Genet.15(23),3459–3472 (2006).
    • 29  Sugden PH, Fuller SJ, Weiss SC, Clerk A: Glycogen synthase kinase 3 (GSK3) in the heart: a point of integration in hypertrophic signaling and a therapeutic target? A critical analysis. Br. J. Pharmacol.153(Suppl. 1),S137–S153 (2008).
    • 30  Urbanek K, Cesselli D, Rota M et al.: Stem cell niches in the adult mouse heart. Proc. Natl Acad. Sci. USA103(24),9226–9231 (2006).
    • 31  Smith RR, Barile L, Cho HC et al.: Regenerative potential of cardiosphere-derived cells expanded from percutaneous endomyocardial biopsy specimens. Circulation115(7),896–908 (2007).
    • 32  Shenje LT, Field LJ, Pritchard CA et al.: Lineage tracing of cardiac explant derived cells. PLoS ONE.3(4),e1929 (2008).
    • 33  Andersen DC, Andersen P, Schneider M, Jensen HB, Sheikh SP: Murine ‘cardiospheres’ are not a source of stem cells with cardiomyogenic potential. Stem Cells27(7),1571–1581 (2009).
    • 34  Bigdeli N, Karlsson C, Strehl R et al.: Coculture of human embryonic stem cells and human articular chondrocytes results in significantly altered phenotype and improved chondrogenic differentiation. Stem Cells27(8),1812–1821 (2009).
    • 35  Moretti A, Caron L, Nakano A et al.: Multipotent embryonic isl1+ progenitor cells lead to cardiac, smooth muscle, and endothelial cell diversification. Cell127(6),1151–1165 (2006).
    • 36  Kwon C, Qian L, Cheng P et al.: A regulatory pathway involving Notch1/β-catenin/Isl1 determines cardiac progenitor cell fate. Nat. Cell Biol.11(8),951–957 (2009).