Young developmental age cardiac extracellular matrix promotes the expansion of neonatal cardiomyocytes in vitro |
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| Institution: | 1. Department of Biomedical Engineering, Tufts University, 4 Colby St., Medford, MA 02155, USA;2. Cellular, Molecular, and Developmental Biology Program, Sackler School for Graduate Biomedical Sciences, Tufts University School of Medicine, Boston, MA 02111, USA;1. i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto 4200-135, Portugal;2. INEB - Instituto de Engenharia Biomédica, Universidade do Porto, Porto 4200-135, Portugal;3. Instituto de Ciências Biomédicas Abel Salazar (ICBAS), Universidade do Porto, Porto 4050-313, Portugal;4. Gladstone Institutes, University of California San Francisco, San Francisco 94158, USA;5. Centre for Ecology, Evolution and Environmental Change, Departamento de Biologia Animal, Faculdade de Ciências, Universidade de Lisboa, Lisboa 1749-016, Portugal;6. Faculty of Medicine, University of Porto, Porto 4200-319, Portugal;7. Unit for Lymphopoiesis, Immunology Department, INSERM U668, University Paris Diderot, Sorbonne Paris Cité, Cellule Pasteur. Institut Pasteur, Paris, France;1. Department of Biomedical Engineering, Tufts University, 4 Colby Street, Medford, MA 02155, USA;2. Molecular, Cellular and Developmental Biology Program, Tufts University School of Medicine, 145 Harrison Ave, Boston, MA 02111, USA;1. Stanford University, Department of Pediatrics, 300 Pasteur Dr., Stanford, CA 94305, USA;2. Sanford-Burnham Medical Research Institute 10901 N. Torrey Pines Road, La Jolla, CA 92037, USA;3. Stanford University, Biomaterials and Advanced Drug Delivery Laboratory, 300 Pasteur Dr., Stanford, CA 94305, USA;1. Australian Regenerative Medicine Institute, Monash University, Clayton, Victoria, Australia;2. Institut für Pharmakologie und Klinische Pharmakologie, University Hospital, Heinrich-Heine-University Düsseldorf, Germany;3. Cardiovascular Research Institute Düsseldorf, University Hospital, Heinrich-Heine-University Düsseldorf, Germany;4. Victor Chang Cardiac Research Institute, Darlinghurst, New South Wales, Australia;5. St. Vincent''s Clinical School, University of New South Wales, Darlinghurst, New South Wales, Australia;6. School of Biotechnology and Biomolecular Science, University of New South Wales, New South Wales, Australia;7. The Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, New York |
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| Abstract: | A major limitation to cardiac tissue engineering and regenerative medicine strategies is the lack of proliferation of postnatal cardiomyocytes. The extracellular matrix (ECM) is altered during heart development, and studies suggest that it plays an important role in regulating myocyte proliferation. Here, the effects of fetal, neonatal and adult cardiac ECM on the expansion of neonatal rat ventricular cells in vitro are studied. At 24 h, overall cell attachment was lowest on fetal ECM; however, ∼80% of the cells were cardiomyocytes, while many non-myocytes attached to older ECM and poly-l-lysine controls. After 5 days, the cardiomyocyte population remained highest on fetal ECM, with a 4-fold increase in number. Significantly more cardiomyocytes stained positively for the mitotic marker phospho-histone H3 on fetal ECM compared with other substrates at 5 days, suggesting that proliferation may be a major mechanism of cardiomyocyte expansion on young ECM. Further study of the beneficial properties of early developmental aged cardiac ECM could advance the design of novel biomaterials aimed at promoting cardiac regeneration. |
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| Keywords: | Cardiac tissue engineering Cardiomyocyte Proliferation Extracellular matrix Second Harmonic Generation imaging |
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