title: Mesenchymal stem cells from fetal heart attenuate myocardial injury after infarction: an in vivo serial pinhole gated SPECT-CT study in rats.
abstract: Mesenchymal stem cells (MSC) have emerged as a potential stem cell type for cardiac regeneration after myocardial infarction (MI). Recently, we isolated and characterized mesenchymal stem cells derived from rat fetal heart (fC-MSC), which exhibited potential to differentiate into cardiomyocytes, endothelial cells and smooth muscle cells in vitro. In the present study, we investigated the therapeutic efficacy of intravenously injected fC-MSC in a rat model of MI using multi-pinhole gated SPECT-CT system. fC-MSC were isolated from the hearts of Sprague Dawley (SD) rat fetuses at gestation day 16 and expanded ex vivo. One week after induction of MI, 2×10(6) fC-MSC labeled with PKH26 dye (n = 6) or saline alone (n = 6) were injected through the tail vein of the rats. Initial in vivo tracking of 99mTc-labeled fC-MSC revealed a focal uptake of cells in the anterior mid-ventricular region of the heart. At 4 weeks of fC-MSC administration, the cells labeled with PKH26 were located in abundance in infarct/peri-infarct region and the fC-MSC treated hearts showed a significant increase in left ventricular ejection fraction and a significant decrease in the end diastolic volume, end systolic volume and left ventricular myo-mass in comparison to the saline treated group. In addition, fC-MSC treated hearts had a significantly better myocardial perfusion and attenuation in the infarct size, in comparison to the saline treated hearts. The engrafted PKH26-fC-MSC expressed cardiac troponin T, endothelial CD31 and smooth muscle sm-MHC, suggesting their differentiation into all major cells of cardiovascular lineage. The fC-MSC treated hearts demonstrated an up-regulation of cardio-protective growth factors, anti-fibrotic and anti-apoptotic molecules, highlighting that the observed left ventricular functional recovery may be due to secretion of paracrine factors by fC-MSC. Taken together, our results suggest that fC-MSC therapy may be a new therapeutic strategy for MI and multi-pinhole gated SPECT-CT system may be a useful tool to evaluate cardiac perfusion, function and cell tracking after stem cell therapy in acute myocardial injury setting.
authors: Stem Cell Research Facility, Department of Hematology, Sanjay Gandhi Post-Graduate Institute of Medical Sciences, Lucknow, India.
authors: Venkata Naga Srikanth
authors: VN
authors: Garikipati
authors: Stem Cell Research Facility, Department of Hematology, Sanjay Gandhi Post-Graduate Institute of Medical Sciences, Lucknow, India.
authors: Sachin
authors: S
authors: Jadhav
authors: Department of Pathology, Sanjay Gandhi Post-Graduate Institute of Medical Sciences, Lucknow, India.
authors: Lily
authors: L
authors: Pal
authors: Cardio-vascular unit, Division of Pharmacology, Central Drug Research Institute, Lucknow, India.
authors: Prem
authors: P
authors: Prakash
authors: Cardio-vascular unit, Division of Pharmacology, Central Drug Research Institute, Lucknow, India.
authors: Madhu
authors: M
authors: Dikshit
authors: Stem Cell Research Facility, Department of Hematology, Sanjay Gandhi Post-Graduate Institute of Medical Sciences, Lucknow, India.
authors: Soniya
authors: S
authors: Nityanand
mesh_terms: D000818:Animals; D055426:Cardiac-Gated Single-Photon Emission Computer-Assisted Tomography; D002454:Cell Differentiation; D002478:Cells, Cultured; D005318:Fetal Heart / Q000166:cytology*; D006352:Heart Ventricles / Q000000981:diagnostic imaging; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D009203:Myocardial Infarction / Q000628:therapy*; D032383:Myocytes, Cardiac / Q000166:cytology / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014057:Tomography, X-Ray Computed; D016276:Ventricular Function