Human umbilical cord blood mesenchymal stem cell transplantation suppresses inflammatory responses and neuronal apoptosis during early stage of focal cerebral ischemia in rabbits.

AIM: Human umbilical cord blood mesenchymal stem cells (hUCB-MSCs) have been shown to ameliorate cerebral ischemia in animal models. In this study we investigated the effects of hUCB-MSCs on inflammatory responses and neuronal apoptosis during the early stage of focal cerebral ischemia in rabbits. METHODS: Focal cerebral ischemia was induced in male New Zealand rabbits by occlusion of MCA for 2 h. The blood samples were collected at different time points prior and during MCAO-reperfusion. The animals were euthanized 3 d after MCAO, and the protein levels of IL-1ß, IL-6, IL-10 and TNF-α in the serum and peri-ischemic brain tissues were detected using Western blot and ELISA, respectively. Inflammatory cell infiltration, neuronal apoptosis and neuronal density were measured morphologically. hUCB-MSCs (5 × 10(6)) were iv injected a few minutes after MCAO. RESULTS: The serum levels of IL-1ß, IL-6 and TNF-α were rapidly increased, and peaked at 2 h after the start of MCAO. hUCB-MSC transplantation markedly and progressively suppressed the ischemia-induced increases of serum IL-1ß, IL-6 and TNF-α levels within 6 h MCAO-reperfusion. Focal cerebral ischemia decreased the serum level of IL-10, which was prevented by hUCB-MSC transplantation. The expression of IL-1ß, IL-6, IL-10 and TNF-α in the peri-ischemic brain tissues showed similar changes as in the serum. hUCB-MSC transplantation markedly suppressed the infiltration of inflammatory cells, and increased the neuronal density around the ischemic region. Furthermore, hUCB-MSC transplantation significantly decreased the percentage of apoptosis around the ischemic region. CONCLUSION: hUCB-MSCs transplantation suppresses inflammatory responses and neuronal apoptosis during the early stage focal cerebral ischemia in rabbits.

Effect of human umbilical cord blood mesenchymal stem cell transplantation on neuronal metabolites in ischemic rabbits.

BACKGROUND: Because there is little research on the effects of transplanted stem cells on neuronal metabolites in infarct areas, we transplanted human umbilical cord blood mesenchymal stem cells (hUCB-MSCs) into cerebral ischemic rabbits and examined the neuronal metabolites. RESULTS: Rabbits (n = 40) were equally divided into sham, middle cerebral artery occlusion (MCAO), hUCB-MSC, and saline groups. The rabbit ischemic model was established by MCAO. The effects of hUCB-MSC transplantation were assessed by proton magnetic resonance spectroscopy (1H-MRS), neurological severity scores (NSSs), infarct area volume, neuronal density, and optical density (OD) of microtubule-associated protein 2 (MAP2)-positive cells. We also evaluated complete blood cell counts(CBCs) and serum biochemical parameters. NSSs in the hUCB-MSC group at 7 and 14 days after reperfusion were lower than in MCAO and saline groups (p < 0.05). Compared with MCAO and saline groups at 2 weeks after MCAO, the infarction volume in the hUCB-MSC group had decreased remarkably (p < 0.05). Significant neuronal metabolic changes occurred in the infarct area at 24 h and 2 weeks after MCAO. 1H-MRS revealed an elevation in the lactate (Lac)/creatine including phosphocreatine (Cr) ratio and a decrease in the N-acetylaspartate (NAA)/Cr and choline-containing phospholipids (Cho)/Cr ratios at 24 h after MCAO in the MCAO group (p < 0.01). Compared with saline and MCAO groups at 24 h and 2 weeks after MCAO, NAA/Cr and Cho/Cr ratios had increased significantly, whereas the Lac/Cr ratio had decreased significantly in the hUCB-MSC group (p < 0.01). Neuronal density and OD of MAP2-positive cells in the MCAO group were significantly lower than those in the sham group, whereas the neuronal density and OD of MAP2-positive cells in the hUCB-MSC group were higher than those in MCAO and saline groups (p < 0.05). CBCs and biochemical parameters were unchanged in the MCAO group at 24 h and 2 weeks after hUCB-MSC transplantation. CONCLUSIONS: Transplanted hUCB-MSCs might ameliorate ischemic damage by influencing neuronal metabolites in the infarct area, providing additional evidence for neuroprotection by stem cells. No significant changes were observed in CBCs or serum biochemical parameters, suggesting that intravenous infusion of hUCB-MSCs is safe for rabbits in the short-term.