Bone marrow stromal cells protect oligodendrocytes from oxygen-glucose deprivation injury.
Oligodendrocyte (OLG) damage leads to demyelination, which is frequently observed in ischemic cerebrovascular diseases. In this study, we investigated the effect of bone marrow stromal cells (BMSCs) on OLGs subjected to oxygen-glucose deprivation (OGD). N20.1 cells (mouse OLG cell line) were transferred into an anaerobic chamber for 3 hr in glucose-free and serum-free medium. After OGD incubation, OLG cultures were divided into the following groups: 1) OGD alone, 2) OLG cocultured with BMSCs, 3) treatment with the phosphoinostide 3-kinase (PI3k) inhibitor LY294002, 4) LY294002-treated OLGs with BMSC cocultured, and 5) anti-p75 antibody-treated OLGs. After an additional 3 hr of reoxygenation incubation, OLG viability and apoptosis were measured. The mRNA expression in the BMSCs and OLGs was analyzed using quantitative real-time PCR (RT-PCR). Serine/threonine-specific protein kinase (Akt), phosphorylated Akt (p-Akt), p75, and caspase 3 protein expressions in OLGs were measured by Western blot. Our results suggest that BMSCs produce growth factors, activate the Akt pathway, and increase the survival of OLGs. BMSCs also reduce p75 and caspase 3 expressions in the OGD-OLGs, which leads to decreased OLG apoptosis. BMSCs participate in OLG protection that may occur with promoting growth factors/PI3K/Akt and inhibiting the p75/caspase pathways. Our study provides insight into white matter damage and the therapeutic benefits of BMSC-based remyelinating therapy after stroke and demyelinating diseases.
Zhang
Jing
J
Department of Neurology, Henry Ford Health System, Detroit, Michigan 48202, USA.
Li
Yi
Y
Zheng
Xuguang
X
Gao
Qi
Q
Liu
Zhongwu
Z
Qu
Runjiang
R
Borneman
Jade
J
Elias
Stanton B
SB
Chopp
Michael
M
D000704:Analysis of Variance; D000818:Animals; D017209:Apoptosis; D001854:Bone Marrow Cells / Q000502:physiology*; D002470:Cell Survival; D002478:Cells, Cultured; D002867:Chromones / Q000494:pharmacology; D018920:Coculture Techniques; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D005947:Glucose / Q000172:deficiency*; D000860:Hypoxia / Q000517:prevention & control*; D020287:In Situ Nick-End Labeling / Q000379:methods; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009025:Morpholines / Q000494:pharmacology; D009836:Oligodendroglia / Q000502:physiology*; D017978:Receptors, Growth Factor / Q000235:genetics / Q000378:metabolism; D017154:Stromal Cells / Q000502:physiology*
D002867:Chromones; D004791:Enzyme Inhibitors; D036341:Intercellular Signaling Peptides and Proteins; D009025:Morpholines; D017978:Receptors, Growth Factor; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D005947:Glucose