Co-transplantation of Hypoxia Pretreated Human Adipose Derived Mesenchymal Stem Cells and Cord Blood Mononuclear Cells to Treat Rats with Acute Myocardial Infarction

Abstract

BackgroundHuman adipose derived mesenchymal stem cells (ASCs) are ideal candidates for the treatment of acute myocardial infarction (AMI), due to their favorable availability and regenerative potential. However, in vivo studies showed that ASCs are not resilient at the infarcted area, for a shortage of blood and oxygen supply. Hypoxic pretreatment was proven to be an effective way to enhance cell survival in ischemic atmosphere. Moreover, co-transplantation of stem cells was another promising strategy to improve cardiac function after transplantation. So, we hypothesized that hypoxic pretreated ASCs combined with proangiogenic cord blood mononuclear cells (CBMNCs) would promote treatment efficacy after co-transplantation.MethodsASCs extracted from male volunteer were preconditioned in hypoxic condition (HP-ASC) for 24h, and total RNA were extracted after that. Gene expressions were compared between HP-ASC and ASC. Then, we transplanted stem cells to female Wistar rats which divided into different groups: (1) HP-ASCs group (n=10, 1x106ASCs); (2) HP-ASCs + CBMNCs group (n=10, 0.5×106 ASCs+0.5×106 CBMNCs); (3) CBMNCs group (n=10, 1×106 ASCs); (4) Control group (n=10, 40μL PBS); (5) Sham group (n=10). Echocardiogram was performed before (0d) and after (30d) after cell transplantation. Hearts were harvested at 30d to analyze the infarct size, myocardium apoptosis, stem cells viability and angiogenesis. ResultsIn vitro study showed that HP-ASCs had a wide range of paracrine function, with the incretion growth factors and their receptors, which would support the cell survivals. In addition, HP-ASCs also gained potentials in hypoxic adaptation (increased expression of HO-1 and SDF-1), as well as homing and immigrating abilities (CXCR4, ICAM-1 and ICAM-2). In vivo studies showed that, 30 days after transplantation in AMI rats, the HP-ASCs group had a better improvement in cardiac function; reduction of the infarct size; and decrease of ASCs death than the other groups (HP-ASCs > HP-ASCs + CBMNCs ≧ CBMNCs > PBS) (p<0.05). However, the combined group of HP-ASCs and CBMNCs had more significant angiogenesis than the other groups (HP-ASCs + CBMNCs > CBMNCs > HP-ASCs > PBS) (p <0.05).ConclusionsHP-ASCs alone had a greater potential in improving cardiac function in AMI rats. However, the combination of HP-ASCs and CBMNCs had a better result in angiogenesis.