title: Viral-mediated fusion of mesenchymal stem cells with cells of the infarcted heart hinders healing via decreased vascularization and immune modulation.
abstract: Cell fusion can occur between mesenchymal stem cells (MSCs) transplanted to improve cardiac function and cells of the recipient. The therapeutic benefit or detriment of resultant cell hybrids is unknown. Here we augment fusion of transplanted MSCs with recipient cardiac cell types via viral fusogens to determine how cardiac function is impacted. Using a Cre/LoxP-based luciferase reporter system coupled to biophotonic imaging and echocardiography, we found that augmenting fusion with the vesicular stomatitis virus glycoprotein (VSVG) increased the amount of fusion in the recipient mouse heart, but led to diminished cardiac function. Specifically, MSCs transfected with VSVG (MSC-VSVG) had the lowest mean fold increase in fractional area change (FAC) and cardiac output (CO). Although the amount of fusion detected had a strong positive correlation (Pearson) with fractional area change and cardiac output at day 7, this effect was lost by day 28. The decrease in cardiac function seen with MSC-VSVG treatment versus MSC alone or sham treatment was associated with decreased MSC retention, altered immune cell responsiveness and reduced vascularization in the heart. This outcome garners consideration in the context of cellular transplantation to damaged tissues, those with viral infection or other microenvironmental conditions that might promote fusion.
authors: Department of Biomedical Engineering, University of Minnesota - Twin Cities, Minneapolis, MN 55455 USA.|Stem Cell Institute, University of Minnesota - Twin Cities, Minneapolis, MN 55455 USA.|Department of Biomedical Engineering, University of Wisconsin - Madison, Madison, WI 53706 USA.
authors: Brian T
authors: BT
authors: Freeman
authors: Department of Biomedical Engineering, University of Minnesota - Twin Cities, Minneapolis, MN 55455 USA.|Stem Cell Institute, University of Minnesota - Twin Cities, Minneapolis, MN 55455 USA.|Department of Biomedical Engineering, University of Wisconsin - Madison, Madison, WI 53706 USA.|Masonic Cancer Center, University of Minnesota - Twin Cities, Minneapolis, MN 55455 USA.|Lillehei Heart Institute, University of Minnesota - Twin Cities, Minneapolis, MN 55455 USA.|Institute for Engineering in Medicine, University of Minnesota - Twin Cities, Minneapolis, MN 55455 USA.
authors: Brenda M
authors: BM
authors: Ogle
mesh_terms: D000818:Animals; D002459:Cell Fusion; D002478:Cells, Cultured; D017930:Genes, Reporter; D006680:HLA Antigens / Q000235:genetics / Q000378:metabolism; D006321:Heart / Q000000981:diagnostic imaging; D000066449:Human Embryonic Stem Cells / Q000166:cytology; D006801:Humans; D007113:Immunity, Innate; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D009203:Myocardial Infarction / Q000000981:diagnostic imaging / Q000628:therapy*; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D018919:Neovascularization, Physiologic; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology; D018116:Vesiculovirus / Q000235:genetics / Q000378:metabolism*; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism; D014945:Wound Healing
chemical_list: D006680:HLA Antigens; D014764:Viral Proteins