Remyelination after Lysophosphatidyl Choline-Induced Demyelination Is Stimulated by Bone Marrow Stromal Cell-Derived Oligoprogenitor Cell Transplantation

Abstract

Bone marrow stromal cells (BMSCs) are a desirable cell source that may be useful for the treatment of neurodegenerative diseases given their capacity to differentiate into various types of cells. The current study aimed to investigate whether oligoprogenitor cell (OPC)-derived BMSCs have therapeutic benefits in an animal model of local demyelination. BMSCs were transdifferentiated into OPCs using a defined culture medium supplemented with a combination of inducers. The differentiation capacity of the BMSCs was evaluated at the end of the induction phase by assessing the expression levels of the glial-specific markers oligodendrocyte transcription factor 2 and O4 surface antigen. Local demyelination was induced in the corpus callosum of adult female rats via direct injection of lysophosphatidylcholine (LPC) followed by engraftment of BMSC-generated OPCs. The rats were divided into sham control, vehicle control, and cell-transplanted groups. The changes in the extent of demyelination and the robustness of the remyelination event were assessed using Luxol Fast Blue staining and immunohistochemical analysis 1 week after LPC injection and 2 weeks after cell transplantation. Consequently, transplantation of OPCs into the demyelinated corpus callosum model resulted in differentiation of the cells into mature oligodendrocytes that were immunopositive for myelin basic protein. Furthermore, OPC transplantation mitigated demyelination and augmented remyelination relative to controls. These findings suggest that BMSC-derived OPCs can be utilized in therapeutic approaches for the management of demyelination-associated diseases such as multiple sclerosis.

Condition medium of cerebrospinal fluid and retinoic acid induces the transdifferentiation of human dental pulp stem cells into neuroglia and neural like cells

“…Therefore, our study showed that adding CSF in culture as inducer medium provided suitable nutrient microenvironment for survival, proliferation and differentiation of hDPSCs. Overall, results of the present study suggest that the cytotoxicity of the CSF will affect the survival rate of the cells in a dose-dependent pattern [202122]. …”

“…It can be noted that BMP4 activate the protein chain called extracellular signal-regulated kinases (ERK). These proteins (ERK) act as signal transmitter from cell surface receptors to the cell nucleus and nucleic acid, leadings to the expression of different enzymes and proteins and providing the neural differentiation of neural progenitor cells [2122232427282930]. …”

“…After three times washes with PBS, appropriate secondary antibodies (donkey anti-rabbit phycoerythrin, ab7007, Abcam System and donkey anti-goat FITC, ab6881, Abcam System) were added for 1 hour at 37℃. Finally, DAPI (Sigma-Aldrich) were used for cell nuclear staining and examined by fluorescent microscopy (Eclipse-TE600, Nikon) [56722]. …”

“…Due to direct contact of CSF with the choroid plexus and neural stem cells in embryonic time, it can accommodate and trade many substances, including growth factors, cytokines, extracellular matrix proteins, adhesion molecules and other active ingredients which are efficient in proliferation and differentiation [2021]. It is demonstrated that of CSF contains many neurotrophic and growth factors [151619202122]. For example, secreted poly-peptides from fetal choroid plexus into the CSF are interlukin-6, ciliary neurotrophic factor (CNTF), transforming growth factor β, nerve growth factor (NGF), insulin growth factor, brain derived neurotrophic factor (BDNF), and neurotrophin 3 which are essential for differentiation, proliferation, repair of nerves and brain development [182122].…”

Clinical application of oligodendrocyte precursor cells for cell-based therapy

“…OPC can be generated from fibroblasts by direct reprogramming[ 25 26 27 ] by ectopic expression of defined transcriptional factors. Induced OPC (iOPC) can expand in vitro and differentiate into mature OL ensheathing host axons and generating compact myelin.…”