Denervated hippocampus provides a favorable microenvironment for neuronal differentiation of endogenous neural stem cells

Fimbria-fornix transection induces both exogenous and endogenous neural stem cells to differentiate into neurons in the hippocampus.This indicates that the denervated hippocampus provides an environment for neuronal differentiation of neural stem cells.However,the pathways and mechanisms in this process are still unclear.Seven days after fimbria fornix transection,our reverse transcription polymerase chain reaction,western blot assay,and enzyme linked immunosorbent assay results show a significant increase in ciliary neurotrophic factor m RNA and protein expression in the denervated hippocampus.Moreover,neural stem cells derived from hippocampi of fetal（embryonic day 17） Sprague-Dawley rats were treated with ciliary neurotrophic factor for 7 days,with an increased number of microtubule associated protein-2-positive cells and decreased number of glial fibrillary acidic protein-positive cells detected.Our results show that ciliary neurotrophic factor expression is up-regulated in the denervated hippocampus,which may promote neuronal differentiation of neural stem cells in the denervated hippocampus.

Human umbilical cord Wharton's Jelly-derived mesenchymal stem cells differentiation into nerve-like cells

Background The two most basic properties of mesenchymal stem cells （MSCs） are the capacities to selfrenew indefinitely and differentiate into multiple cells and tissue types. The cells from human umbilical cord Wharton＇ s Jelly have properties of MSCs and represent a rich source of primitive cells. This study was conducted to explore the possibility of inducing human umbilical cord Wharton＇ s Jelly-derived MSCs to differentiate into nerve-like cells.Methods MSCs were cultured from the Wharton＇ s Jelly taken from human umbilical cord of babies delivered after full-term normal labor. Salvia miltiorrhiza and [3-mercaptoethanol were used to induce the human umbilical cord-derived MSCs to differentiate The expression of neural protein markers was shown by immunocytochemistry. The induction process was monitored by phase contrast microscopy, electron microscopy （EM）, and laser scanning confocal microscopy （LSCM） . The pleiotrophin and nestin genes were measured by reverse transcription-polymerase chain reaction （RT-PCR）.Results MSCs in the Wharton＇ s Jelly were easily attainable and could be maintained and expanded in culture. They were positive for markers of MSCs, but negative for markers of hematopoietic cells and graft-versus-host disease （GVHD）-related cells. Treatment with Salvia mihiorrhiza caused Wharton＇ s Jelly cells to undergo profound morphological changes. The induced MSCs developed rounded cell bodies with multiple neurite-like extensions. Eventually they developed processes that formed networks reminiscent of primary cultures of neurons. Salvia mihiorrhiza and β-mercaptoethanol also induced MSCs to express nestin, β-tubulin Ⅲ, neurofilament （NF） and glial fibrillary acidic protein （GFAP）. It was confirmed by RT-PCR that MSCs could express pleiotrophin both before and after induction by Salvia miltiorrhiza. The expression was markedly enhanced after induction and the nestin gene was also expressed.Conclusions MSCs could be isolated from human umbilical cord Wharton＇ s Jelly. They were capable ofdifferentiating into nerve-like cells using Salvia miltiorrhiza or 15-mercaptoethanol. The induced MSCs not only underwent morphologic changes, but also expressed the neuron-related genes and neuronal cell markers. They may represent an alternative source of stem cells for central nervous system cell transplantation.