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Durable scar size reduction due to allogeneic mesenchymal stem cell therapy regulates whole-chamber remodeling.

Publication ,  Journal Article
Williams, AR; Suncion, VY; McCall, F; Guerra, D; Mather, J; Zambrano, JP; Heldman, AW; Hare, JM
Published in: J Am Heart Assoc
May 17, 2013

BACKGROUND: Intramyocardial injection of mesenchymal stem cells (MSCs) in chronic ischemic cardiomyopathy is associated with reverse remodeling in experimental models and humans. Here, we tested the hypothesis that allogeneic MSC therapy drives ventricular remodeling by producing durable and progressive scar size reduction in ischemic cardiomyopathy. METHODS AND RESULTS: Gottingen swine (n=12) underwent left anterior descending coronary artery myocardial infarction (MI), and 3 months post-MI animals received either intramyocardial allogeneic MSC injection (200 mol/L cells; n=6) or left ventricle (LV) catheterization without injection (n=6). Swine were followed with serial cardiac magnetic resonance imaging for 9 months to assess structural and functional changes of the LV. Intramyocardial injection was performed using an integrated imaging platform combining electroanatomical mapping unipolar voltage and 3-dimensional cardiac magnetic resonance imaging angiography-derived anatomy to accurately target infarct border zone injections. MSC-treated animals had a 19.62 ± 2.86% reduction in scar size at 3 months postinjection, which progressed to 28.09 ± 2.31% from 3 to 6 months postinjection (P<0.0001). MSC-treated animals had unchanged end-diastolic volume (EDV; P=0.08) and end-systolic volume (ESV; P=0.28) from preinjection to 6 months postinjection, whereas controls had progressive dilatation in both EDV (P=0.0002) and ESV (P=0.0002). In addition, MSC-treated animals had improved LV sphericity index. Percentage change in infarct size correlated with percentage change in EDV (r=0.68; P=0.01) and ESV (r=0.77; P=0.001). Ejection fraction increased from 29.69 ± 1.68% to 35.85 ± 2.74% at 3 months post-MSC injection and progressed to 39.02 ± 2.42% 6 months postinjection (P=0.0001), whereas controls had a persistently depressed ejection fraction during follow-up (P=0.33). CONCLUSION: Intramyocardial injection of allogeneic MSCs leads to a sustained and progressive reduction in infarct size, which in turn drives reverse remodeling and increases in ejection fraction. These findings support ongoing biological activity of cell therapy for substantial periods and suggest optimal end points for future clinical trials.

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Published In

J Am Heart Assoc

DOI

EISSN

2047-9980

Publication Date

May 17, 2013

Volume

2

Issue

3

Start / End Page

e000140

Location

England

Related Subject Headings

  • Ventricular Remodeling
  • Swine, Miniature
  • Swine
  • Mesenchymal Stem Cell Transplantation
  • Magnetic Resonance Imaging
  • Female
  • Cicatrix
  • Animals
  • 3201 Cardiovascular medicine and haematology
  • 1102 Cardiorespiratory Medicine and Haematology
 

Citation

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Williams, A. R., Suncion, V. Y., McCall, F., Guerra, D., Mather, J., Zambrano, J. P., … Hare, J. M. (2013). Durable scar size reduction due to allogeneic mesenchymal stem cell therapy regulates whole-chamber remodeling. J Am Heart Assoc, 2(3), e000140. https://doi.org/10.1161/JAHA.113.000140
Williams, Adam R., Viky Y. Suncion, Frederic McCall, Danny Guerra, Jacques Mather, Juan P. Zambrano, Alan W. Heldman, and Joshua M. Hare. “Durable scar size reduction due to allogeneic mesenchymal stem cell therapy regulates whole-chamber remodeling.J Am Heart Assoc 2, no. 3 (May 17, 2013): e000140. https://doi.org/10.1161/JAHA.113.000140.
Williams AR, Suncion VY, McCall F, Guerra D, Mather J, Zambrano JP, et al. Durable scar size reduction due to allogeneic mesenchymal stem cell therapy regulates whole-chamber remodeling. J Am Heart Assoc. 2013 May 17;2(3):e000140.
Williams, Adam R., et al. “Durable scar size reduction due to allogeneic mesenchymal stem cell therapy regulates whole-chamber remodeling.J Am Heart Assoc, vol. 2, no. 3, May 2013, p. e000140. Pubmed, doi:10.1161/JAHA.113.000140.
Williams AR, Suncion VY, McCall F, Guerra D, Mather J, Zambrano JP, Heldman AW, Hare JM. Durable scar size reduction due to allogeneic mesenchymal stem cell therapy regulates whole-chamber remodeling. J Am Heart Assoc. 2013 May 17;2(3):e000140.
Journal cover image

Published In

J Am Heart Assoc

DOI

EISSN

2047-9980

Publication Date

May 17, 2013

Volume

2

Issue

3

Start / End Page

e000140

Location

England

Related Subject Headings

  • Ventricular Remodeling
  • Swine, Miniature
  • Swine
  • Mesenchymal Stem Cell Transplantation
  • Magnetic Resonance Imaging
  • Female
  • Cicatrix
  • Animals
  • 3201 Cardiovascular medicine and haematology
  • 1102 Cardiorespiratory Medicine and Haematology