ABSTRACT
Lithium has been shown to inhibit apoptosis of neural progenitor cells (NPCs) and promote differentiation of NPCs. However, there was rare data to discuss the effects of lithium on neural differentiation of mesenchymal stem cells (MSCs). Here, we investigated the potential promotion of lithium to MSC proliferation and neural differentiation in vitro and after transplanted into the ventral horn of rat spinal cord in vivo. We found that lithium possesses the ability to promote proliferation of GFP-MSCs in a dose dependent manner as verified by growth curve and bromodeoxyuridine (BrdU) incorporation assays; While in neural induction medium, lithium (0.1 mM) promotes neural differentiation of GFP-MSCs as verified by immunostaining and quantitative analysis. After transplantation of GFP-MSCs into the rat spinal cord, lithium treatment enhanced cell survival and neural differentiation after transplantation as verified by immunohistochemistry. These data suggested that lithium could be a potential drug to augment the therapeutic efficiency of MSCs transplantation therapy in central nervous system (CNS) disorders.
Subject(s)
Cell Proliferation/drug effects , Lithium Chloride/pharmacology , Mesenchymal Stem Cell Transplantation , Mesenchymal Stem Cells/drug effects , Neural Stem Cells/drug effects , Neural Stem Cells/transplantation , Neurogenesis/drug effects , Spinal Cord/surgery , Animals , Cell Lineage , Cell Survival/drug effects , Cells, Cultured , Dose-Response Relationship, Drug , Female , Genes, Reporter , Graft Survival/drug effects , Green Fluorescent Proteins/biosynthesis , Green Fluorescent Proteins/genetics , Immunohistochemistry , Mesenchymal Stem Cells/metabolism , Neural Stem Cells/metabolism , Phenotype , Rats, Sprague-Dawley , Spinal Cord/metabolism , Time Factors , TransfectionABSTRACT
OBJECTIVE: To observe the effects of neural stem cells (NSCs) transplantation on the brain derived neurotrophic factor (BDNF) after the spinal cord injury (SCI) of rats, and to investigate the mechanism of repairing the SCI by NSCs transplantation. METHODS: Neural stem cells were cultured from the hippocampus of rats' embryo and identified by immunocytochemistry. Seven days after the operation of SCI, the NSCs were transplanted into the injured site. Sixty adult Wistar rats were randomly divided into three groups: SCI cured with NSCs transplantation (group A), SCI received DMEM solution (group B), control group (group C). Then the expression of BDNF of the lesion and neighbor areas were examined by reverse transcsription polymerase chain reaction (RT-PCR) and immunohistochemistry, so as to investigated the mechanism of repairing the SCI after NSCS transplantation. RESULTS: According the RT-PCR results analysis, the expression of BDNF mRNA of group A enhanced higher than that of group B on the 1st, 3rd, 5th day after transplantation of NSCs. According the immunohistochemistry results analysis, the expression of BDNF mRNA of group A enhanced higher than that of group B on the 7th, 14th, 28th day similarly. CONCLUSION: The transplantation of NSCs can change the tiny-entironment by upregulating the expression of BDNF. It maybe one of the mechanism of repairing the SCI by NSCs transplantation.
