Improved conduction and increased cell retention in healed MI using mesenchymal stem cells suspended in alginate hydrogel

Nikhil C. Panda, Sean T. Zuckerman, Olurotimi O. Mesubi, David S. Rosenbaum, Marc S. Penn, J. Kevin Donahue, Eben Alsberg, Kenneth R. Laurita

Research output: Contribution to journalArticle

Abstract

Introduction: Mesenchymal stem cells (MSCs) have been associated with reduced arrhythmias; however, the mechanism of this action is unknown. In addition, limited retention and survival of MSCs can significantly reduce efficacy. We hypothesized that MSCs can improve impulse conduction and that alginate hydrogel will enhance retention of MSCs in a model of healed myocardial infarction (MI).

Methods and results: Four weeks after temporary occlusion of the left anterior descending artery (LAD), pigs (n = 13) underwent a sternotomy to access the infarct and then were divided into two studies. In study 1, designed to investigate impulse conduction, animals were administered, by border zone injection, 9–15 million MSCs (n = 7) or phosphate-buffered saline (PBS) (control MI, n = 5). Electrogram width measured in the border zone 2 weeks after injections was significantly decreased with MSCs (−30 ± 8 ms, p < 0.008) but not in shams (4 ± 10 ms, p = NS). Optical mapping from border zone tissue demonstrated that conduction velocity was higher in regions with MSCs (0.49 ± 0.03 m/s) compared to regions without MSCs (0.39 ± 0.03 m/s, p < 0.03). In study 2, designed to investigate MSC retention, animals were administered an equal number of MSCs suspended in either alginate (2 or 1 % w/v) or PBS (n = 6/group) by border zone injection. Greater MSC retention and survival were observed with 2 % alginate compared to PBS or 1 % alginate. Confocal immunofluorescence demonstrated that MSCs survive and are associated with expression of connexin-43 (Cx43) for either PBS (control), 1 %, or 2 % alginate.

Conclusions: For the first time, we are able to directly associate MSCs with improved impulse conduction and increased retention and survival using an alginate scaffold in a clinically relevant model of healed MI.

Original languageEnglish (US)
Pages (from-to)117-127
Number of pages11
JournalJournal of Interventional Cardiac Electrophysiology
Volume41
Issue number2
DOIs
StatePublished - Oct 8 2014

Keywords

  • Alginate
  • Biomaterials
  • Cardiac regeneration
  • Conduction velocity
  • Connexin 43
  • Electrograms
  • Electrophysiology
  • Impulse conduction
  • Impulse propagation
  • Large animal model
  • Mesenchymal stem cells
  • Myocardial infarction
  • Myocardial scar
  • Optical mapping
  • Slow conduction
  • Stem cell engraftment
  • Sudden death
  • Ventricular tachycardia

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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