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Enhanced effect of combining human cardiac stem cells and bone marrow mesenchymal stem cells to reduce infarct size and to restore cardiac function after myocardial infarction.

Publication ,  Journal Article
Williams, AR; Hatzistergos, KE; Addicott, B; McCall, F; Carvalho, D; Suncion, V; Morales, AR; Da Silva, J; Sussman, MA; Heldman, AW; Hare, JM
Published in: Circulation
January 15, 2013

BACKGROUND: Because mesenchymal stem cells (MSCs) induce proliferation and differentiation of c-kit(+) cardiac stem cells (CSCs) in vivo and in vitro, we hypothesized that combining human (h) MSCs with c-kit(+) hCSCs produces greater infarct size reduction compared with either cell administered alone after myocardial infarction (MI). METHODS AND RESULTS: Yorkshire swine underwent balloon occlusion of the left anterior descending coronary artery followed by reperfusion and were immunosuppressed after MI with cyclosporine and methylprednisolone. Intramyocardial combination hCSCs/hMSCs (1 million cells/200 million cells, n=5), hCSCs alone (1 million cells, n=5), hMSCs alone (200 million cells, n=5), or placebo (phosphate-buffered saline; n=5) was injected into the infarct border zones at 14 days after MI. Phenotypic response to cell therapy was assessed by cardiac magnetic resonance imaging and micromanometer conductance catheterization hemodynamics. Although each cell therapy group had reduced MI size relative to placebo (P<0.05), the MI size reduction was 2-fold greater in combination versus either cell therapy alone (P<0.05). Accompanying enhanced MI size reduction were substantial improvement in left ventricular chamber compliance (end-diastolic pressure-volume relationship; P<0.01) and contractility (preload recruitable stroke work and dP/dtmax; P<0.05) in combination-treated swine. Ejection fraction was restored to baseline in cell-treated pigs, whereas placebo pigs had persistently depressed left ventricular function (P<0.05). Immunohistochemistry showed 7-fold enhanced engraftment of stem cells in the combination therapy group versus either cell type alone (P<0.001). CONCLUSIONS: Combining hMSCs and hCSCs as a cell therapeutic enhances scar size reduction and restores diastolic and systolic function toward normal after MI. Taken together, these findings illustrate important biological interactions between c-kit(+) CSCs and MSCs that enhance cell-based therapeutic responses.

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Published In

Circulation

DOI

EISSN

1524-4539

Publication Date

January 15, 2013

Volume

127

Issue

2

Start / End Page

213 / 223

Location

United States

Related Subject Headings

  • Ventricular Function, Left
  • Treatment Outcome
  • Transplantation, Heterologous
  • Systole
  • Sus scrofa
  • Recovery of Function
  • Proto-Oncogene Proteins c-kit
  • Myocytes, Cardiac
  • Myocardial Infarction
  • Mesenchymal Stem Cells
 

Citation

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Williams, A. R., Hatzistergos, K. E., Addicott, B., McCall, F., Carvalho, D., Suncion, V., … Hare, J. M. (2013). Enhanced effect of combining human cardiac stem cells and bone marrow mesenchymal stem cells to reduce infarct size and to restore cardiac function after myocardial infarction. Circulation, 127(2), 213–223. https://doi.org/10.1161/CIRCULATIONAHA.112.131110
Williams, Adam R., Konstantinos E. Hatzistergos, Benjamin Addicott, Fred McCall, Decio Carvalho, Viky Suncion, Azorides R. Morales, et al. “Enhanced effect of combining human cardiac stem cells and bone marrow mesenchymal stem cells to reduce infarct size and to restore cardiac function after myocardial infarction.Circulation 127, no. 2 (January 15, 2013): 213–23. https://doi.org/10.1161/CIRCULATIONAHA.112.131110.
Williams AR, Hatzistergos KE, Addicott B, McCall F, Carvalho D, Suncion V, et al. Enhanced effect of combining human cardiac stem cells and bone marrow mesenchymal stem cells to reduce infarct size and to restore cardiac function after myocardial infarction. Circulation. 2013 Jan 15;127(2):213–23.
Williams, Adam R., et al. “Enhanced effect of combining human cardiac stem cells and bone marrow mesenchymal stem cells to reduce infarct size and to restore cardiac function after myocardial infarction.Circulation, vol. 127, no. 2, Jan. 2013, pp. 213–23. Pubmed, doi:10.1161/CIRCULATIONAHA.112.131110.
Williams AR, Hatzistergos KE, Addicott B, McCall F, Carvalho D, Suncion V, Morales AR, Da Silva J, Sussman MA, Heldman AW, Hare JM. Enhanced effect of combining human cardiac stem cells and bone marrow mesenchymal stem cells to reduce infarct size and to restore cardiac function after myocardial infarction. Circulation. 2013 Jan 15;127(2):213–223.

Published In

Circulation

DOI

EISSN

1524-4539

Publication Date

January 15, 2013

Volume

127

Issue

2

Start / End Page

213 / 223

Location

United States

Related Subject Headings

  • Ventricular Function, Left
  • Treatment Outcome
  • Transplantation, Heterologous
  • Systole
  • Sus scrofa
  • Recovery of Function
  • Proto-Oncogene Proteins c-kit
  • Myocytes, Cardiac
  • Myocardial Infarction
  • Mesenchymal Stem Cells