Abstract： Objective To investigate the effect of combinational hypothermia on growth and proliferation of temperature sensitive stem cells in hypoxia microenvironment after traumatic brain injury (TBI).Methods Temperature sensitive human umbilical cord mesenchymal stem cell line (tsUCMSCs) was generated and labeled by BrdU.In vivo study,severe traumatic brain injury mice model was established by fluid percussion.Then,PBS,UCMSCs or tsUCMSCs was implanted into injured region,and normothermia or mild hypothermia therapy (33℃) was adopt.The expression of BrdU in post -injury area was examined by immunohistochemistry.In vitro study,hypoxia or low serum in low metling agarose gel model was used,by which UCMSCs or tsUCMSCs in 33℃ or 37℃ was cultured.Cell number was counted with hematocytometer and PCNA or caspase 3 was measured with immunofluorecent staining.The level of hypoxia - inducible factor - 1 α ( HIF - 1 α) in vitro and in vivo was examined by western blot.Results The BrdU- positive cells in post - injury area at 7d of transplantation were significantly increased in combinational tsUCMSCs and hypothermia group.Compared with cells in 37℃,cells in 33℃ showed more cell number,more PCNA and less caspase 3 expression in hypoxia or low serum culture condition,among of which tsUCMSCs in 33℃ group showed the most enhancement of cell number and PCNA or the most decrease of caspase 3.The level of HIF - 1α was elevated both in vitro and in vivo model.Conclusion Combination of tsUCMSCs and hypothermia could increase the ability of grafted stem cells adapting to the hypoxia microenvironment and facilitate more survival of transplanted stem cells after TBI.This combinational therapy may provide a new and feasible strategy for TBI.