Mechanisms underlying remyelination with special focus on demyelination models of multiple sclerosis / 浙江大学学报·医学版

Failure to remyelinate and rewrap the demyelinated axons has been revealed as the major hurdle for treatment of multiple sclerosis (MS), and the bottleneck is the inability of oligodendrocyte progenitor cell (OPC) to differentiate into mature oligodendrocyte. Remyelination is a spontaneous regenerative process, which includes activation, migration and differentiation of OPC, and is believed to protect the axon and further halt neurodegeneration. In recent years, studies have identified many potential drug targets for efficiently promoting OPC differentiation in demyelination models, such as metformin, clemostine, and drug targets as myelin transcription factor 1-like protein (Myt1L), N-methyl-D-aspartic acid (NMDA) receptor, connexin 43 (Cx43), G protein coupled receptor 17 (GPR17), κ opioid receptor (KOR), sterol 14α-demethylase (CYP51), Δ14-sterol reductase (TM7SF2), emopamil-binding protein (EBP). This review summarizes the recent progress on the mechanisms underlying the activation, migration and differentiation of OPC in remyelination with special focus on studies using demyelination models of MS, which may provide insights of further exploring new therapeutic strategies for MS.

Morphological changes in human oligodendrocyte progenitor cells during passage / 中国组织工程研究

BACKGROUND: Oligodendrocyte precursor cells are seed cells for the treatment of white matter injury. The establishment of an efficient and stable in vitro culture method is an important prerequisite for clinical transformation. OBJECTIVE: To investigate the morphological changes of oligodendrocyte precursor cells during passage. METHODS: Four batches of human oligodendrocyte progenitor cells were subcultured from the second generation (P2) to the seventh generation (P7) in vitro. Five pictures of 200-fold field were taken under an optical microscope before each passage. According to the cell morphology, oligodendrocyte precursor cells were divided into three types: bipolar cells (oligodendrocyte precursor cells), multipolar cells (late oligodendrocyte precursor cells) and supra-polar bifurcated cells (immature oligodendrocyte cells). The proportion of oligodendrocyte progenitor cells to the total number of cells was calculated, so as to compare the difference of cell morphology among different generations. RESULTS AND CONCLUSION: In the process of passage from P2 to P7, oligodendrocyte progenitor cells included three types: bipolar cells, multipolar cells and supra-polar bifurcated cells. Among them, bipolar cells and multipolar cells were the main part, and a small number of supra-polar bifurcated cells could be seen in the rest. There were no significant differences in the proportion of bipolar cells, multipolar cells and supra-polar bifurcated cells among P2-P7 (P > 0.05). The cell morphology classification and counting method can be used to preliminarily evaluate that oligodendrocyte progenitor cells have no change in morphology during culture.

Research progress of glioma cell origin / 中国病理生理杂志

Glioma,a common primary brain tumor, is considered to be incurable, and easy to relapse.The median survival of the patients with glioma after treatment is only 15 to 19 months.The high heterogeneity of glioma is the main reason leading to poor clinical treatment,and the underlying mechanism is closely related to the cell origin of glioma. Therefore,to elucidate the cell origin of glioma is important to further study the mechanism of tumor formation and develop effective treatment programs.For a long time,studies have attempted to speculate on the cell origin of glioma based on the morphological characteristics,but agreements still haven't been reached.This review focuses on the most probable origin cells,such as neural stem cells,astrocytes,oligodendrocyte progenitor cells and neurons.

Adult mesenchymal stem cell therapy for myelin repair in Multiple Sclerosis

Multiple sclerosis (MS) is a demyelinating immune-mediated disease of the central nervous system (CNS). It is the most frequent neurological disease in young adults and affects over 2 million people worldwide. Current treatments reduce the relapse rate and the formation of inflammatory lesions in the CNS, but with only temporary and limited success. Despite the presence of endogenous oligodendroglial progenitors (OPCs) and of spontaneous remyelination, at least in early MS its levels and its qualities are apparently insufficient for a sustained endogenous functional repair. Therefore, novel MS therapies should consider not only immunemodulatory but also myelin repair activities. Mesenchymal stem cells (MSCs) represent an attractive alternative to develop a cell-based therapy for MS. MSCs display stromal features and exert bystander immunemodulatory and neuroprotective activities. Importantly, MSCs induce oligodendrocyte fate decision and differentiation/maturation of adult neural progenitors, suggesting the existence of MSC-derived remyelination activity. Moreover, transplanted MSCs promote functional recovery and myelin repair in different MS animal models. Here, we summarize the current knowledge on endogenous mechanisms for remyelination and proposed autologous MSC therapy as a promising strategy for MS treatment.

Isolation and identification of oligodendrocyte progenitor cells from neonatal rats / 第三军医大学学报

Objective To develop new methods to cultivate, retrieve and purify oligodendrocyte progenitor cells (OPCs). Methods Primary OPCs were isolated from mixed glial cultures of newborn Sprague Dawley rat forebrains by using a selective detachment procedure, further purified by differential adhesion, and maintained in a chemical conditioned medium. The characteristic of OPCs was determined by both electrophysiological recording and immunostaining. Results Immunocytochemical analysis revealed that more than 90% of the isolated cells expressed the OPCs-specific marker NG2. OPCs exhibited a moderate input resistance, delayed rectifier K+ currents (IK) that could be antagonized partly by TEA-Cl and CsCl, small tetrodotoxin (TTX) sensitive Na+ currents that failed to generate typical action potentials. Conclusion Isolation and purification by selective detachment and differential adhesion procedure are effective to obtain highly purified OPCs. OPCs, distinct from neuron, astrocyte, oligodendrocyte or microglia, possess unique physiological properties.