ABSTRACT
BACKGROUND: Bone marrow mesenchymal stem cells improve neurological functional recovery from cerebral infarction, but they are a rare population in the bone marrow with difficulty in cell separation and purification. OBJECTIVE: To investigate the neuroprotective effects and the potential mechanisms of human placenta-derived mesenchymal stem cell transplantation for cerebral infarction in rats. METHODS: Totally 120 rats subjected to middle cerebral artery occlusion were randomized into treatment group and control (n=60 per group). The rats were intravenously treated with human placenta-derived mesenchymal stem cells in the treatment group or the phosphate buffer saline in the control group. Then, a modified neurological severity score was assessed at 1, 3, 7, 14 days post transplantation, and measurement of infarct volume in the ischemic brain was performed using 2,3,5-triphenyltetrazolium chloride staining at 14 days post transplantation. The anti-human specific immunostain for mitochondria in the ischemic brain was performed and the mitochondria-positive cells were counted; TUNEL immunostaining was performed and TUNEL positive cells were counted. ELISA assays for brain-derived neurotrophic factor (BDNF), vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF) were also performed in the ischemic brain. RESULTS AND CONCLUSION: At 1, 3, 7 and 14 days after treatment, the modified neurological severity score in the treatment group was significantly lower than that in the control group (P < 0.05). At 14 days after treatment, the infarct volume in the treatment group was significantly lower than that in the control group (P < 0.05), only few mitochondria-positive cells were present in the ischemic brain, and the number of TUNEL positive cells in the treatment group was significantly less than that in the control group (P < 0.05). At 3 and 14 days after treatment, BDNF expression levels in the treatment group were significantly higher than those in the control group (P < 0.05). At 7 and 14 days after treatment, VEGF expression levels in the treatment group were significantly higher than those in the control (P < 0.05). At 7 days after treatment, HGF expression level in the treatment group was significantly higher than that in the control group (P < 0.05). To conclude, intravenous administration of human placenta-derived mesenchymal stem cells can promote neuroprotective effects against cerebral infarction. These effects may be related to the increase of BDNF, VEGF and HGF expression and the decrease of apoptosis in the ischemic brain.
ABSTRACT
<p><b>BACKGROUND</b>Mesenchymal stem cells (MSCs) transplantation is of therapeutic potential after ischemic injury in both experimental and clinical studies. Clinically, elderly patients are more vulnerable to acute myocardial infarction (AMI). But little is known about the characteristics of young donor-derived MSCs transplanted to old patients with AMI. The present study was designed to investigate the effect of transplanted MSCs from rats of different ages on the improvement of heart function after AMI.</p><p><b>METHODS</b>MSCs from Sprague-Dawley (SD) rats were isolated and cultured in vitro. The apoptosis characteristics of MSCs were observed under conditions of ischemia and anoxia. SD rats underwent MI received intramyocardial injection of MSCs from young donor rats (n = 8), old donor rats (n = 8), respectively. AMI control group received equal volume physiological saline. Immunofluorescence was used to observe the differentiation of the grafted cells into cardiomyocytes. Four weeks after cell transplantation, reverse transcriptase-polymerase chain reaction (RT-PCR) and immunohistochemistry for vascular endothelial growth factor (VEGF), VIII-factor immunohistochemistry for vessel density, TUNEL, caspase-3 for cardiomyocyte apoptosis, echocardiography and hemodynamic detection for heart function were performed.</p><p><b>RESULTS</b>The apoptosis rate of the old donor-derived MSCs group was significantly higher than that of the young donor-derived MSCs group under conditions of ischemia and anoxia (P < 0.05). Engrafted MSCs survived, proliferated and differentiated into myocardium-like cells. VEGF gene expression and capillary density in the old donor-derived group were lower than those in the young donor-derived group but higher than those in the control group (P < 0.05). The transplantation of old donor-derived MSCs attenuated apoptosis of cardiomyocytes in the peri-infarct region compared with the control group and the effect was elevated in young donor-derived MSCs (P < 0.05). The heart functions (left ventricle ejection fraction (LVEF), left ventricle fractional shortening (LVFS)) were improved more significantly in the old donor-derived MSCs group than in the control group and the heart function in the young donor-derived MSCs group further improved (P < 0.05).</p><p><b>CONCLUSIONS</b>Young donor-derived MSCs can improve heart function significantly through angiogenesis and decreasing cardiomyocyte apoptosis when transplanted to the infarcted area.</p>