Human Umbilical Cord Blood Mesenchymal Stem Cells Transplantation Modulate Inflammatory Response And Display Neuroprotection At Early Stage In Focal Cerebral-reperfusion Of Rabbits

ObjectiveTo observe the effect of human umbilical cord blood mesenchymal stem cells(hUCB-MSCs) transplantation on inflammatory response and neuroprotection at earlystage in focal cerebral-reperfusion of rabbits.MethodshUCB-MSCs extracted from80~100ml cord blood from full-term infants withinformed maternal consent were cultured in vitro. In total of sixty-four male NewZealand rabbits were randomly allocated into four groups: ischemia-reperfusiongroup(IR)(n=16), hUCB-MSCs treated group (IR+hUCB-MSC)(n=16), normalsaline-treated group (IR+NS)(n=16), sham group(SH)(n=16). The rabbit ischemicmodel was established by middle cerebral artery occlusion (MCAO). hUCB-MSCs (5×106) diluted in3mL PBS were injected slowly for five min via the right leg femoral veinin the hUCB-MSCs group. For the saline group,3mL PBS without hUCB-MSCs wereinjected in a manner identical to the hUCB-MSCs group.To evaluate the effect of hUCB-MSCs on inflammatory response, IL-1β, IL-6, IL-10and TNF-α protein expression were detected at early stage of ischemia. Inflammatorycells infiltration, ischemic cortical neuronal apoptosis, Purdy scale, serum NGF andBDNF levels，cortical neuronal MAP2were also measured in each group. ResultsSerum levels of IL-1β and IL-6increased after cerebral ischemia and reached the peakat2h after reperfusion. Serum levels of IL-1β, IL-6and TNF-α in IR+hUCB-MSCgroup were obviously lower than that of IR and IR+NS group at each time point(P<0.05, respectively). On the contrary, serum level of IL-10decreased after cerebralischemia. Serum level of IL-10in IR+hUCB-MSC group was much more high than thatof IR and IR+NS group after reperfusion (P <0.05, respectively). Westernblot resultsstrengthened the serum level finding at the3d. hUCB-MSC therapy amelioratedmarkedly the infiltration of inflammatory cells around ischemic region（P＜0.05）.At3d after MCAO, there were multiple apoptotic cells in IR and IR+NS group. The AIin IR group was obviously increased. The IR+hUCB-MSC group had a lower AI thanthe IR or IR+NS group (P <0.05, respectively). The serum content of NGF,BDNF andischemic cortical neuronal MAP2in IR+hUCB-MSC group twere much higher han thatof IR or IR+NS group (P<0.05). The Purdy scale scores in IR+hUCB-MSC group wasmuch lower than that of IR or IR+NS group (P＜0.05).Conclusion1. hUCB-MSCs treatment could modulate inflammatory response at early stage in focalischemia of rabbits.2. hUCB-MSCs treatment could inhibit cortical apoptosis in focal ischemia of rabbits.3. hUCB-MSCs treatment could increase the serum content of neurotrophic factors andpromote the regeneration of neurons.4. hUCB-MSCs treatment could improve the neurological function in focal ischemia of rabbits.