Cord blood CD133+ cell transplantation improves cognitive function and survival of transgenic mice with dementia / 中国组织工程研究

ABSTRACT

BACKGROUND:Human umbilical cord blood (CB)-derived CD133+ cells are a minority population of primitive cells with extensive proliferation and differentiation potentials,which are considered to have ability of neural differentiation.OBJECTIVE:We hypothesized a possible application of CB CD133+ cells in the cognitive and survival function of mice with dementia,the present study observed the changes of the cognitive function and survival of amyloid precursor protein(APP)transgenic mice after CB CD 133+ cells transplantation to verify the above assumption.DESIGN,TIME AND SETTING:A completely randomized block design of animal experiments was performed in the Hematology Institute of Tianjin Hematology Hospital from September 2005 to December 2007.MATERIALSForty-eight eight-month-old male APP 695 transgenic C57BL/6 (BDF1/KM) mice were selected in this experiments All mice were divided randomly into three groupscontrol group (n=8),CD133+ transplantation group (n=20) and CD133 transplantation group (n=20).METHODS:Mice in control groups received an intraventricular injection of 10 μL phosphate buffered saline (PBS).The transgenic mice that received an intraventricular injection of 10 μL CD133+ (5×104/μL) and CD133 CB cells (5×104/μL) respectively.MAIN OUTCOME MEASURES:Radial ann water maze (RAWM) was used to evaluate cognitive function of the mice and the survival days of mice in different groups were recorded,lmmunohistochemical assessments and Dil Fluorescence labeled way was used to detect the differentiation phenotype of transplanted cells.RESULTS:The cognitive function of the mice in CD133+ transplantation group was significantly improved compared with the mice in CD 133- transplantation and control groups both 30 and 180 days after transplantation (P＜0.05).The mean survival time of the mice in CD133+ transplantation group was significantly increased compared with CD133 transplantin group and control group (P＜0.05).It was observed that the transplantation CB CD133+ cells labeled with Dil migrated into several brain regions at day 30 post-transplantation.These cells were stained for human βⅢ-tubulin,neuralfilement(NF),neuron specific enolase (NSE),and glial fibriliary acidic protein(GFAP).However,in the brain of mice that received CD133 cells transplantation,CB cells were distributed mainly in and around the lateral ventricle at day 30 and 180 post-transplantation and GFAP-,βⅢ-tubulin- and NSE-positive cells were rarely detected.After intraventricular transplantation of CB CD133+ cells,the percentage of transplanted Dil-labeled CB cells expressing βⅢ-tubulin was significant higher at day 30 than at day 180,and the percentage of CB cells expressing NSE was significant lower at day 30 than that at day 180 (both P＜0.01).The percentage of CB cells expressing GFAP was relatively constant between the days 30 and 180 after transplantation (P＞0.05).CONCLUSION:The result of this experiment suggested that the cognitive and survival function improvement achieved by transplantation of CB CD133+ cells is mainly due to a replacement of dysfunctional cells or augmentation of neural circuit by CB CD133+ cells transplantation.