In vitro assessment of the direct effect of laquinimod on basic functions of human neural stem cells and oligodendrocyte progenitor cells

2014 ◽  
Vol 346 (1-2) ◽  
pp. 66-74 ◽  
Author(s):  
Eve E. Kelland ◽  
Wendy Gilmore ◽  
Liat Hayardeny ◽  
Leslie P. Weiner ◽  
Brett T. Lund
2019 ◽  
Vol 41 (1-2) ◽  
pp. 79-93 ◽  
Author(s):  
Shen Li ◽  
Jiao Zheng ◽  
Linlin Chai ◽  
Mengsi Lin ◽  
Ruocheng Zeng ◽  
...  

Oligodendrocyte progenitor cells (OPCs) may have beneficial effects in cell replacement therapy of neurodegenerative disease owing to their unique capability to differentiate into myelinogenic oligodendrocytes (OLs) in response to extrinsic signals. Therefore, it is of significance to establish an effective differentiation methodology to generate highly pure OPCs and OLs from some easily accessible stem cell sources. To achieve this goal, in this study, we present a rapid and efficient protocol for oligodendroglial lineage differentiation from mouse neural stem cells (NSCs), rat NSCs, or mouse embryonic stem cell-derived neuroepithelial stem cells. In a defined culture medium containing Smoothened Agonist, basic fibroblast growth factor, and platelet-derived growth factor-AA, OPCs could be generated from the above stem cells over a time course of 4–6 days, achieving a cell purity as high as ∼90%. In particular, these derived OPCs showed high expandability and could further differentiate into myelin basic protein-positive OLs within 3 days or alternatively into glial fibrillary acidic protein-positive astrocytes within 7 days. Furthermore, transplantation of rodent NSC-derived OPCs into injured spinal cord indicated that it is a feasible strategy to treat spinal cord injury. Our results suggest a differentiation strategy for robust production of OPCs and OLs from rodent stem cells, which could provide an abundant OPC source for spinal cord injury.


2013 ◽  
Vol 2 (10) ◽  
pp. 731-744 ◽  
Author(s):  
Christopher J. Sontag ◽  
Hal X. Nguyen ◽  
Noriko Kamei ◽  
Nobuko Uchida ◽  
Aileen J. Anderson ◽  
...  

2016 ◽  
Vol 14 (2) ◽  
pp. 1316-1322 ◽  
Author(s):  
Pan Yang ◽  
Yun-Qian Guan ◽  
Ya-Li Li ◽  
Li Zhang ◽  
Lan Zhang ◽  
...  

2011 ◽  
Vol 8 (11) ◽  
pp. 957-962 ◽  
Author(s):  
Fadi J Najm ◽  
Anita Zaremba ◽  
Andrew V Caprariello ◽  
Shreya Nayak ◽  
Eric C Freundt ◽  
...  

2012 ◽  
Vol 287 (15) ◽  
pp. 12529-12540 ◽  
Author(s):  
Pei-Shan Wang ◽  
Jing Wang ◽  
Yi Zheng ◽  
Catherine J. Pallen

Tightly controlled termination of proliferation determines when oligodendrocyte progenitor cells (OPCs) can initiate differentiation and mature into myelin-forming cells. Protein-tyrosine phosphatase α (PTPα) promotes OPC differentiation, but its role in proliferation is unknown. Here we report that loss of PTPα enhanced in vitro proliferation and survival and decreased cell cycle exit and growth factor dependence of OPCs but not neural stem/progenitor cells. PTPα−/− mice have more oligodendrocyte lineage cells in embryonic forebrain and delayed OPC maturation. On the molecular level, PTPα-deficient mouse OPCs and rat CG4 cells have decreased Fyn and increased Ras, Cdc42, Rac1, and Rho activities, and reduced expression of the Cdk inhibitor p27Kip1. Moreover, Fyn was required to suppress Ras and Rho and for p27Kip1 accumulation, and Rho inhibition in PTPα-deficient cells restored expression of p27Kip1. We propose that PTPα-Fyn signaling negatively regulates OPC proliferation by down-regulating Ras and Rho, leading to p27Kip1 accumulation and cell cycle exit. Thus, PTPα acts in OPCs to limit self-renewal and facilitate differentiation.


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