Mouse heart showing position of coronary arteries Credit: NIMR, MRC. Wellcome Images
People with advanced heart failure often live out the rest of their lives hoping that a donor heart might become available, and even if one does it’s often difficult for the recipient’s body to accept the new organ. Growing new hearts from stem cells may open the possibility of producing personalized organs that have an ideal size and shape, but more importantly that will not be rejected when transplanted.
Researchers at the University of Pittsburgh School of Medicine have taken a major step toward that goal by successfully populating a decellularized mouse heart with human multipotential cardiovascular progenitor (MCP) cells and actually making it beat. A special procedure was used to wash out the original cardiomyocytes from the mouse heart, leaving only the organ’s empty structural matrix. They then seeded the empty matrix with MCPs derived from fibroblast cells taken from a skin biopsy that were first turned into pluripotent stem cells. The MCPs can then differentiate into three different types of heart cells, which they did with seeming guidance from the matrix, and after a few weeks the new “heart” began to beat at between 40 and 50 bpms. The researchers believe that this technology should allow for creation of healthy heart tissue, or perhaps entire hearts, that could revolutionize how advanced heart disease is treated.
From the study in Nature Communications:
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.
Study in Nature Communications: Repopulation of decellularized mouse heart with human induced pluripotent stem cell-derived cardiovascular progenitor cells
