Recent research found that human umbilical cord is rich in mesenchymal stem cells. These cells have the potencies of expressing many surface markers of mesenchymal stem cell and of differentiating into a variety of cells of three germ layers, synthesizing and secreting a set of trophic factors and other cytokines, and supporting the expansion and function of other cells hematopoietic stem cells and other cells. In addition, immunogenicity of these cells is realatively low.

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.MATERIALS:Forty-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 groups:control 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.

BACKGROUND: At present, hemopoietic stem cells have been proved to differentiate into nerves in rodents animals. As for the human, this topic is in debate.OBJECTIVE: To investigate the neural differentiation potential of human umbilical cord blood-derived AC133+ cells. DESIGN, TIME AND SETTING: Control experiments by grouping were performed in the Hematology Institute of Tianjin Hematology Hospital and Central Laboratory of Neurosurgery in Yuquan Hospital of Tsinghua University from August 2005 to December 2007.MATERIALS: Human umbilical cord blood was sampled from full-term newborn infant. Fetal brain-derived trophic support cells were harvested from aborted fetus of 22 weeks old.MAIN OUTCOME MEASURES: After the induction, human cord blood cells were collected at weeks 1, 2 and 4. RT-PCR was used to detect the expression of nestin, bone morphogenetic protein-2 and neural cell adhesion molecule. Immunocytochemistry method was applied to detect the cytotype-specific antigen. RESULTS: In the culture medium containing epidermal growth factor and basic fibroblast growth factor, human cord blood AC133+ cells could express nestin and bone morphogenetic protein-2, which were down-regulated even closed up in suboptimal condition. In the DMEM/F12 medium supplemented with epidermal growth factor, basic fibroblast growth factor and brain-derived neurotrophic factor, the gene expression of bone morphogenetic protein-2 and nestin continued in optimal condition at 2 weeks. Moreover neural cell adhesion molecule, another gene of neural cells, also expressed in this condition. AC133+ cells co-cultured with fetal brain-derived trophic support cells exhibited similar expressions. In the optimal non-cell-cell contact co-culture system, glial fibrillary acidic protein-positive cells were found by immuocytochemistry, while neuronal marker β-tubulin Ⅲwas expressed in the cell-cell direct contact system. These outcomes indicated that human cord blood isolated AC133+ cells may have an effect through gene rearrangement on inducing stem cells to express nerve cell development factors.CONCLUSION: The human umbilical cord blood-derived AC133+ cells contain some multipotential stem cells with differentiation potential, neural differentiation-related antigen when exposed to a suitable microenvironment.