Optical mapping of cryoinjured rat myocardium grafted with mesenchymal stem cells.
Mesenchymal stem cells (MSCs) have been shown to improve cardiac electrophysiology when administered in the setting of acute myocardial infarction. However, the electrophysiological phenotype of MSCs in situ is not clear. We hypothesize that MSCs delivered intramyocardially to cryoinjured myocardium can engraft, but will not actively generate, action potentials. Cryoinjury-induced scar was created on the left ventricular epicardial surface of adult rat hearts. Within 30 min, hearts were injected with saline (sham, n = 11) or bone marrow-derived MSCs (2 × 10(6)) labeled with 1,1'-dioctadecyl-3,3,3,3'-tetramethylindocarbocyanine percholate (DiI; n = 16). At 3 wk, optical mapping and cell isolation were used to measure optical action potentials and calcium transients, respectively. Histological analysis confirmed subepicardial scar thickness and the presence of DiI-positive cells that express connexin-43. Optical action potential amplitude within the scar at MSC-positive sites (53.8 ± 14.3%) was larger compared with sites devoid of MSCs (35.3 ± 14.2%, P < 0.05) and sites within the scar of shams (33.5 ± 6.9%, P < 0.05). Evidence of simultaneous action potential upstroke, the loss of action potential activity following ablation of adjacent viable myocardium, and no rapid calcium transient response in isolated DiI+ cells suggest that the electrophysiological influence of engrafted MSCs is electrotonic. MSCs can engraft when directly injected into a cryoinjury and are associated with evidence of action potential activity. However, our results suggest that this activity is not due to generation of action potentials, but rather passive influence coupled from neighboring viable myocardium.
MetroHealth Campus, Case Western Reserve University, Cleveland, Ohio, USA.
Andrea R
AR
Costa
Nikhil C
NC
Panda
Sandro
S
Yong
Maritza E
ME
Mayorga
Gary P
GP
Pawlowski
KeKe
K
Fan
Marc S
MS
Penn
Kenneth R
KR
Laurita
D000200:Action Potentials; D000818:Animals; D020013:Calcium Signaling; D002232:Carbocyanines; D002450:Cell Communication; D018031:Connexin 43 / Q000378:metabolism; D003452:Cryosurgery; D004195:Disease Models, Animal; D005456:Fluorescent Dyes; D006329:Heart Conduction System / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D006352:Heart Ventricles / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D009203:Myocardial Infarction / Q000175:diagnosis / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000601:surgery*; D009206:Myocardium / Q000378:metabolism / Q000473:pathology*; D051381:Rats; D011917:Rats, Inbred Lew; D012038:Regeneration; D013997:Time Factors; D056969:Voltage-Sensitive Dye Imaging
D002232:Carbocyanines; D018031:Connexin 43; D005456:Fluorescent Dyes; C024286:3,3'-dioctadecylindocarbocyanine