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Bioengineering Human Myocardium on Native Extracellular Matrix.

Jacques P Guyette1, Jonathan M Charest1, Robert W Mills1

  • 1From the Center for Regenerative Medicine (J.P.G., J.M.C., B.J.J., P.T.M., S.E.G., T.O., G.G., H.C.O.), Cardiovascular Research Center (R.W.M., D.J.M.), Division of Cardiology (D.J.M.), and Division of Thoracic Surgery, Department of Surgery (H.C.O.), Massachusetts General Hospital, Boston, MA; Harvard Medical School, Boston, MA (J.P.G., B.J.J., P.T.M., S.E.G., G.G., H.C.O.); Department of Biomedical Engineering, Worcester Polytechnic Institute, Worcester, MA (J.R.G., G.R.G.); and Harvard Stem Cell Institute, Cambridge, MA (H.C.O.).

Circulation Research
|October 28, 2015
PubMed
Summary
This summary is machine-generated.

Researchers bioengineered functional human myocardial tissue using native cardiac extracellular matrix and human stem cell-derived cardiomyocytes. This approach offers a potential alternative to heart transplantation for treating heart failure.

Keywords:
cardiomyocytesextracellular matrixinduced pluripotent stem cellsregeneration

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Area of Science:

  • Regenerative Medicine
  • Biomaterials Science
  • Cardiovascular Research

Background:

  • Heart failure affects over 25 million worldwide, with limited donor hearts for transplantation.
  • Donor organ scarcity and rejection are significant challenges in current heart transplant procedures.
  • Bioartificial myocardium from patient cells presents a theoretical alternative for heart failure treatment.

Purpose of the Study:

  • To engineer functional human myocardial tissue at a clinically relevant scale.
  • To utilize human induced pluripotent stem cell-derived cardiomyocytes and native human cardiac matrix.
  • To develop a potential alternative to allogeneic heart transplantation.

Main Methods:

  • Human acellular cardiac scaffolds were created using perfusion-decellularization, preserving extracellular matrix and vasculature.
  • Human induced pluripotent stem cell-derived cardiomyocytes were used to repopulate these scaffolds.
  • Constructs were cultured for 120 days to assess structural and functional development.

Main Results:

  • Engineered cardiac tissues exhibited sarcomeric structure, cell/matrix deformation, contractile force, and electrical conduction.
  • Human whole-heart scaffolds were partially recellularized, developing force-generating myocardial tissue.
  • The bioengineered constructs demonstrated electrical conductivity, left ventricular pressure development, and metabolic function.

Conclusions:

  • Native cardiac extracellular matrix scaffolds support human induced pluripotent stem cell-derived cardiomyocyte engraftment.
  • Functional human myocardial-like tissue of various complexities can be bioengineered.
  • This platform shows promise for developing patient-specific cardiac tissue grafts.