Migration and differentiation of exogenous rat mesenchymal stem cells engrafted into normal and injured hearts of rats

Abstract

To investigate the effects of different microcircumstances on the migration and differentiation of grafted rat mesenchymal stem cells (rMSC) in host myocardium and the feasibility of treatment of myocardial infarction by exogenous adult stem cells. rMSC were isolated from the femurs and tibiae of a male Wistar rat and then purified, made into cell suspension, and labeled with DAPI. 35 female Wistar rat were divided randomly into four groups: acute myocardial infarction control group (AMI group, n = 10, the descending anterior branch of left coronary artery was ligated), acute myocardial infarction + rMSC transplantation group (AMI + rMSC group, n = 10, 1 - 3 hours after the ligation DAPI-labeled rMSC were injected into the peri-infarct tissues), normal heart + rMSC transplantation group (normal heart + MSC group, n = 10, DAPI-labeled rMSC were injected into the corresponding myocardium), and mono-nuclear cells transplantation group (AMI + MNCS, n = 5 DAPI-labeled mononuclear cells were injected into he periinfarct tissues). Ten weeks after the implantation, the rats were killed and their hearts were harvested. Immunohistochemistry was used to examine the troponin, GATA-4 and connexin-43. No lymphocyte proliferation and immonologic rejection were seen in the cardiac tissues of the rats implanted with rMSC. DAPI-labeled rMSC with blue nuclei were distributed extensively in the myocardium of the AMI + rMSC group, ovoid in shape and arranged in parallel with the cardiac muscle fibers, and were distributed sporadically like islands in the myocardium of the normal heart + rMSC group, irregular in shape and not arranged in parallel with the cardiac muscle fibers. No blue nucleus was seen in the cardiac tissues of the hearts implanted with DAPI-labeled mononuclear cells. Troponin and GATA4 were positive immunohistochemically in the implanted rMSC with blue nuclei and the host cardiac muscle cells of the AMI group and AMI + rMSC group, however, were negative in the implanted rMSC with blue nuclei and normal cardiac muscle cells of the normal heart + rMSC group. Purified rMSC are immunologically tolerable and can be used as donor cells for exogenous cells therapy. Capable of surviving and homing in both in normal and injured hearts, exogenous rMSC migrate and differentiate into cardiac muscle cell-like cells in myocardium with infarction, however, not in normal heart.