Mesenchymal Stem Cells from Fetal Heart Attenuate Myocardial Injury after Infarction: An In Vivo Serial Pinhole Gated SPECT-CT Study in Rats

PLoS One

Prem Prakash¹  Madhu Dikshit¹  Lily Pal²  Sachin Jadhav³  Soniya Nityanand³  Venkata Naga Srikanth Garikipati³ 

[1] Cardio-vascular unit, Division of Pharmacology, Central Drug Research Institute, Lucknow, India;Department of Pathology, Sanjay Gandhi Post-Graduate Institute of Medical Sciences, Lucknow, India;Stem Cell Research Facility, Department of Hematology, Sanjay Gandhi Post-Graduate Institute of Medical Sciences, Lucknow, India

关键词: Heart;    Myocardial infarction;    Mesenchymal stem cells;    Stem cell therapy;    Muscle differentiation;    Single photon emission computed tomography;    Cardiovascular physiology;    Myocardium;   

DOI  :  10.1371/journal.pone.0100982

学科分类：医学（综合）

来源: Public Library of Science

【 摘 要 】

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, 2×106 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.

【 授权许可】

CC BY