title: Stem cell therapy enhances electrical viability in myocardial infarction.
abstract: Clinical studies suggest increased arrhythmia risk associated with cell therapy for myocardial infarction (MI); however, the underlying mechanisms are poorly understood. We hypothesize that the degree of electrical viability in the infarct and border zone associated with skeletal myoblast (SKMB) or mesenchymal stem cell (MSC) therapy will determine arrhythmia vulnerability in the whole heart. Within 24 h of LAD ligation in rats, 2 million intramyocardially injected SKMB (n=6), intravenously infused MSC (n=7), or saline (n=7) was administered. One month after MI, cardiac function was determined and novel optical mapping techniques were used to assess electrical viability and arrhythmia inducibility. Shortening fraction was greater in rats receiving SKMB (17.8%+/-5.3%, p=0.05) or MSC (17.6%+/-3.0%, p<0.01) compared to MI alone (10.1%+/-2.2%). Arrhythmia inducibility score was significantly greater in SKMB (2.8+/-0.2) compared to MI (1.4+/-0.5, p=0.05). Inducibility score for MSC (0.6+/-0.4) was significantly lower than SKMB (p=0.01) and tended to be lower than MI. Optical mapping revealed that MSC therapy preserved electrical viability and impulse propagation in the border zone, but SKMB did not. In addition, injected SKMBs were localized to discrete cell clusters where connexin expression was absent. In contrast, infused MSCs engrafted in a more homogeneous pattern and expressed connexin proteins. Even though both MSC and SKMB therapy improved cardiac function following MI in rat, SKMB therapy significantly increased arrhythmia inducibility while MSC therapy tended to lower inducibility. In addition, only MSC therapy was associated with enhanced electrical viability, diffuse engraftment, and connexin expression, which may explain the differences in arrhythmia inducibility.
authors.affiliation: The Heart and Vascular Research Center, MetroHealth Campus, Case Western Reserve University, Cleveland, OH 44109, USA.
authors.forename: William R
authors.initials: WR
authors.lastname: Mills
authors.forename: Niladri
authors.initials: N
authors.lastname: Mal
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Kiedrowski
authors.forename: Ryan
authors.initials: R
authors.lastname: Unger
authors.forename: Farhad
authors.initials: F
authors.lastname: Forudi
authors.forename: Zoran B
authors.initials: ZB
authors.lastname: Popovic
authors.forename: Marc S
authors.initials: MS
authors.lastname: Penn
authors.forename: Kenneth R
authors.initials: KR
authors.lastname: Laurita
mesh_terms: D000818:Animals; D001145:Arrhythmias, Cardiac / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000628:therapy; D002470:Cell Survival; D022062:Electrophysiologic Techniques, Cardiac; D006085:Graft Survival; D006329:Heart Conduction System / Q000473:pathology / Q000503:physiopathology; D045164:Mesenchymal Stem Cell Transplantation; D032448:Myoblasts, Skeletal / Q000378:metabolism / Q000637:transplantation*; D009203:Myocardial Infarction / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D051381:Rats; D020127:Recovery of Function; D014184:Transplantation, Homologous