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

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Journal of Interventional Cardiac Electrophysiology Aims and scope Submit manuscript

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.

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Acknowledgments

Funding for this project was provided by NIH Grant RC1HL100105 (KRL).

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Authors and Affiliations

  1. Heart & Vascular Research Center, MetroHealth Campus of Case Western Reserve University, 2500, MetroHealth Drive, Rammelkamp, 6th floor, Cleveland, OH, 44109-1998, USA

    Nikhil C. Panda, Olurotimi O. Mesubi, David S. Rosenbaum, J. Kevin Donahue & Kenneth R. Laurita

  2. Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH, USA

    Sean T. Zuckerman

  3. Departments of Biomedical Engineering and Orthopaedic Surgery, Case Western Reserve University, Cleveland, OH, USA

    Eben Alsberg

  4. Summa Cardiovascular Institute, Summa Health System, Akron, OH, USA

    Marc S. Penn

Authors
  1. Nikhil C. Panda
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  2. Sean T. Zuckerman
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  3. Olurotimi O. Mesubi
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  4. David S. Rosenbaum
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  8. Kenneth R. Laurita
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Correspondence to Kenneth R. Laurita.

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Panda, N.C., Zuckerman, S.T., Mesubi, O.O. et al. Improved conduction and increased cell retention in healed MI using mesenchymal stem cells suspended in alginate hydrogel. J Interv Card Electrophysiol 41, 117–127 (2014). https://doi.org/10.1007/s10840-014-9940-9

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  • DOI: https://doi.org/10.1007/s10840-014-9940-9

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