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Related Experiment Video

Updated: Feb 27, 2026

Construction of a Multilayered Mesenchymal Stem Cell Sheet with a 3D Dynamic Culture System
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Layered smooth muscle cell-endothelial progenitor cell sheets derived from the bone marrow augment postinfarction

Yasuhiro Shudo1, Andrew B Goldstone1, Jeffrey E Cohen1

  • 1Department of Cardiothoracic Surgery, Stanford University School of Medicine, Stanford, Calif.

The Journal of Thoracic and Cardiovascular Surgery
|June 28, 2017
PubMed
Summary

This study demonstrates that a novel cell sheet therapy combining endothelial progenitor cells (EPCs) and smooth muscle cells (SMCs) promotes blood vessel formation and improves heart function after myocardial infarction.

Keywords:
cell sheetmyocardial infarctionneovascularizationregenerationstem cellstissue engineering

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Area of Science:

  • Regenerative Medicine
  • Cardiovascular Biology
  • Biomaterials Engineering

Background:

  • Endothelial progenitor cells (EPCs) are crucial for new blood vessel formation.
  • The angiogenic potential of EPCs may be limited by the absence of supportive cells like smooth muscle cells (SMCs).
  • Mimicking native blood vessel architecture could enhance EPC function.

Purpose of the Study:

  • To investigate the efficacy of a novel bone marrow-derived cell sheet composed of EPCs and SMCs.
  • To assess its potential to limit adverse ventricular remodeling post-myocardial infarction.
  • To evaluate its capacity to promote angiogenesis and improve cardiac function.

Main Methods:

  • Isolated primary EPCs and mesenchymal stem cells from Wistar rat bone marrow.
  • Transdifferentiated mesenchymal stem cells into SMCs and co-cultured them with EPCs to form a bi-level cell sheet.
  • Transplanted the SMC-EPC cell sheet into a rodent model of ischemic cardiomyopathy.

Main Results:

  • Cell sheet therapy showed a trend towards increased mature vessel density.
  • Significantly attenuated cardiac fibrosis in treated animals compared to controls.
  • Improved left ventricular ejection fraction and reduced ventricular dimensions post-infarction.

Conclusions:

  • A spatially arranged SMC-EPC bi-level cell sheet derived from bone marrow is a novel therapeutic approach.
  • The interaction between SMCs and EPCs in the cell sheet enhances neovascularization.
  • This therapy effectively limits adverse cardiac remodeling and improves ventricular function after myocardial infarction.