title: Improved conduction and increased cell retention in healed MI using mesenchymal stem cells suspended in alginate hydrogel.
abstract: BACKGROUND
  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).
  
  
  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.
authors.affiliation: Heart & Vascular Research Center, MetroHealth Campus of Case Western Reserve University, 2500, MetroHealth Drive, Rammelkamp, 6th floor, Cleveland, OH, 44109-1998, USA.
authors.forename: Nikhil C
authors.initials: NC
authors.lastname: Panda
authors.forename: Sean T
authors.initials: ST
authors.lastname: Zuckerman
authors.forename: Olurotimi O
authors.initials: OO
authors.lastname: Mesubi
authors.forename: David S
authors.initials: DS
authors.lastname: Rosenbaum
authors.forename: Marc S
authors.initials: MS
authors.lastname: Penn
authors.forename: J Kevin
authors.initials: JK
authors.lastname: Donahue
authors.forename: Eben
authors.initials: E
authors.lastname: Alsberg
authors.forename: Kenneth R
authors.initials: KR
authors.lastname: Laurita
mesh_terms: D000464:Alginates / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D018929:Cell Culture Techniques; D002478:Cells, Cultured; D004195:Disease Models, Animal; D015150:Echocardiography, Doppler / Q000379:methods; D004562:Electrocardiography / Q000379:methods; D022062:Electrophysiologic Techniques, Cardiac; D020723:Glucuronic Acid / Q000494:pharmacology; D006329:Heart Conduction System / Q000502:physiology*; D006603:Hexuronic Acids / Q000494:pharmacology; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000494:pharmacology; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D018613:Microscopy, Confocal; D009203:Myocardial Infarction / Q000000981:diagnostic imaging / Q000473:pathology / Q000628:therapy*; D011897:Random Allocation; D012016:Reference Values; D013552:Swine; D016896:Treatment Outcome
chemical_list: D000464:Alginates; D006603:Hexuronic Acids; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D020723:Glucuronic Acid