Modulation of human mesenchymal stem cell function in a three-dimensional matrix promotes attenuation of adverse remodelling after myocardial infarction

David L. Simpson, Samuel C. Dudley

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

The application of tissue engineering (TE) practices for cell delivery offers a unique approach to cellular cardiomyoplasty. We hypothesized that human mesenchymal stem cells (hMSCs) applied to the heart in a collagen matrix would outperform the same cells grown in a monolayer and directly injected for cardiac cell replacement after myocardial infarction in a rat model. When hMSC patches were transplanted to infarcted hearts, several measures for left ventricle (LV) remodelling and function were improved, including fractional area change, wall thickness, -dP/dt and LV end-diastolic pressure. Neovessel formation throughout the LV infarct wall after hMSC patch treatment increased by 37% when compared to direct injection of hMSCs. This observation was correlated with increased secretion of angiogenic factors, with accompanying evidence that these factors enhanced vessel formation (30% increase) and endothelial cell growth (48% increase) in vitro. These observations may explain the in vivo observations of increased vessel formation and improved cardiac function with patch-mediated cell delivery. Although culture of hMSC in collagen patches enhanced angiogenic responses, there was no effect on cell potency or viability. Therefore, hMSCs delivered as a cardiac patch showed benefits above those derived from monolayers and directly injected. hMSCs cultured and delivered within TE constructs may represent a good option to maximize the effects of cellular cardiomyoplasty.

Original languageEnglish (US)
Pages (from-to)192-202
Number of pages11
JournalJournal of Tissue Engineering and Regenerative Medicine
Volume7
Issue number3
DOIs
StatePublished - Mar 2013
Externally publishedYes

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Stem cells
Mesenchymal Stromal Cells
Myocardial Infarction
Modulation
Cardiomyoplasty
Tissue Engineering
Tissue engineering
Collagen
Heart Ventricles
Monolayers
Ventricular Remodeling
Angiogenesis Inducing Agents
Endothelial cells
Direct injection
Cell growth
Cell culture
Rats
Endothelial Cells
Cells
Blood Pressure

Keywords

  • Cell therapy
  • Mesenchymal stem cells
  • Myocardial infarction
  • Neovascularization
  • Paracrine effect
  • Tissue engineering

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Biomaterials
  • Biomedical Engineering

Cite this

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abstract = "The application of tissue engineering (TE) practices for cell delivery offers a unique approach to cellular cardiomyoplasty. We hypothesized that human mesenchymal stem cells (hMSCs) applied to the heart in a collagen matrix would outperform the same cells grown in a monolayer and directly injected for cardiac cell replacement after myocardial infarction in a rat model. When hMSC patches were transplanted to infarcted hearts, several measures for left ventricle (LV) remodelling and function were improved, including fractional area change, wall thickness, -dP/dt and LV end-diastolic pressure. Neovessel formation throughout the LV infarct wall after hMSC patch treatment increased by 37{\%} when compared to direct injection of hMSCs. This observation was correlated with increased secretion of angiogenic factors, with accompanying evidence that these factors enhanced vessel formation (30{\%} increase) and endothelial cell growth (48{\%} increase) in vitro. These observations may explain the in vivo observations of increased vessel formation and improved cardiac function with patch-mediated cell delivery. Although culture of hMSC in collagen patches enhanced angiogenic responses, there was no effect on cell potency or viability. Therefore, hMSCs delivered as a cardiac patch showed benefits above those derived from monolayers and directly injected. hMSCs cultured and delivered within TE constructs may represent a good option to maximize the effects of cellular cardiomyoplasty.",
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