Repopulation of decellularized mouse heart with human induced pluripotent stem cell-derived cardiovascular progenitor cells

Tung-Ying Lu, Bo Lin, Jong Kim, Mara Sullivan, Kimimasa Tobita, Guy Salama and Lei Yang ()
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Tung-Ying Lu: University of Pittsburgh School of Medicine, Rangos Research Center
Bo Lin: University of Pittsburgh School of Medicine, Rangos Research Center
Jong Kim: Heart and Vascular Institute, University of Pittsburgh, School of Medicine
Mara Sullivan: CBI, University of Pittsburgh
Kimimasa Tobita: University of Pittsburgh School of Medicine, Rangos Research Center
Guy Salama: Heart and Vascular Institute, University of Pittsburgh, School of Medicine
Lei Yang: University of Pittsburgh School of Medicine, Rangos Research Center

Nature Communications, 2013, vol. 4, issue 1, 1-11

Abstract: Abstract Heart disease is the leading cause of death in the world. Heart tissue engineering holds a great promise for future heart disease therapy by building personalized heart tissues. Here we create heart constructs by repopulating decellularized mouse hearts with human induced pluripotent stem cell-derived multipotential cardiovascular progenitor cells. We show that the seeded multipotential cardiovascular progenitor cells migrate, proliferate and differentiate in situ into cardiomyocytes, smooth muscle cells and endothelial cells to reconstruct the decellularized hearts. After 20 days of perfusion, the engineered heart tissues exhibit spontaneous contractions, generate mechanical force and are responsive to drugs. In addition, we observe that heart extracellular matrix promoted cardiomyocyte proliferation, differentiation and myofilament formation from the repopulated human multipotential cardiovascular progenitor cells. Our novel strategy to engineer personalized heart constructs could benefit the study of early heart formation or may find application in preclinical testing.

Date: 2013
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DOI: 10.1038/ncomms3307

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