scholarly journals MicroRNA-219 Inhibits Proliferation and Induces Differentiation of Oligodendrocyte Precursor Cells after Contusion Spinal Cord Injury in Rats

2019 ◽  
Vol 2019 ◽  
pp. 1-13 ◽  
Author(s):  
Fang Li ◽  
Mou-Wang Zhou ◽  
Nan Liu ◽  
Yan-Yan Yang ◽  
Hua-Yi Xing ◽  
...  

MicroRNA-219 (miR-219) regulates the proliferation and differentiation of oligodendrocyte precursor cells (OPCs) during central nervous system (CNS) development. OPCs only differentiate into oligodendrocytes (OLs) in the healthy CNS, but can generate astrocytes (As) after injury. We hypothesized that miR-219 may modulate OPC proliferation and differentiation in a cervical C5 contusion spinal cord injury (SCI) model. After injury, we observed a decrease in the miR-219 level and quantity of OLs and an increase in the number of OPCs and As. Silencing of miR-219 by its antagomir in vivo produced similar results, but of greater magnitude. Overexpression of miR-219 by its agomir in vivo increased the number of OLs and suppressed generation of OPCs and As. Luxol fast blue staining confirmed that SCI caused demyelination and that the extent of demyelination was attenuated by miR-219 overexpression, but aggravated by miR-219 reduction. Monocarboxylate transporter 1 (MCT-1) may be implicated in the regulation of OPC proliferation and differentiation mediated by miR-219 following contusion SCI. Collectively, our data suggest that miR-219 may mediate SCI-induced OPC proliferation and differentiation, and MCT-1 may participate in this process as a target of miR-219.

2017 ◽  
Vol 37 (43) ◽  
pp. 10290-10309 ◽  
Author(s):  
Toru Doi ◽  
Toru Ogata ◽  
Junji Yamauchi ◽  
Yasuhiro Sawada ◽  
Sakae Tanaka ◽  
...  

2015 ◽  
Vol 2015 ◽  
pp. 1-20 ◽  
Author(s):  
Ning Li ◽  
Gilberto K. K. Leung

Spinal cord injury (SCI) is a devastating condition to individuals, families, and society. Oligodendrocyte loss and demyelination contribute as major pathological processes of secondary damages after injury. Oligodendrocyte precursor cells (OPCs), a subpopulation that accounts for 5 to 8% of cells within the central nervous system, are potential sources of oligodendrocyte replacement after SCI. OPCs react rapidly to injuries, proliferate at a high rate, and can differentiate into myelinating oligodendrocytes. However, posttraumatic endogenous remyelination is rarely complete, and a better understanding of OPCs’ characteristics and their manipulations is critical to the development of novel therapies. In this review, we summarize known characteristics of OPCs and relevant regulative factors in both health and demyelinating disorders including SCI. More importantly, we highlight current evidence on post-SCI OPCs transplantation as a potential treatment option as well as the impediments against regeneration. Our aim is to shed lights on important knowledge gaps and to provoke thoughts for further researches and the development of therapeutic strategies.


2020 ◽  
Vol 2020 ◽  
pp. 1-15
Author(s):  
Alexander Younsi ◽  
Guoli Zheng ◽  
Moritz Scherer ◽  
Lennart Riemann ◽  
Hao Zhang ◽  
...  

Stem cell therapy with neural precursor cells (NPCs) has the potential to improve neuroregeneration after spinal cord injury (SCI). Unfortunately, survival and differentiation of transplanted NPCs in the injured spinal cord remains low. Growth factors have been successfully used to improve NPC transplantation in animal models, but their extensive application is associated with a relevant financial burden and might hinder translation of findings into the clinical practice. In our current study, we assessed the potential of a reduced number of growth factors in different combinations and concentrations to increase proliferation and differentiation of NPCs in vitro. After identifying a “cocktail” (EGF, bFGF, and PDGF-AA) that directed cell fate towards the oligodendroglial and neuronal lineage while reducing astrocytic differentiation, we translated our findings into an in vivo model of cervical clip contusion/compression SCI at the C6 level in immunosuppressed Wistar rats, combining NPC transplantation and intrathecal administration of the growth factors 10 days after injury. Eight weeks after SCI, we could observe surviving NPCs in the injured animals that had mostly differentiated into oligodendrocytes and oligodendrocytic precursors. Moreover, “Stride length” and “Average Speed” in the CatWalk gait analysis were significantly improved 8 weeks after SCI, representing beneficial effects on the functional recovery with NPC transplantation and the administration of the three growth factors. Nevertheless, no effects on the BBB scores could be observed over the course of the experiment and regeneration of descending tracts as well as posttraumatic myelination remained unchanged. However, reactive astrogliosis, as well as posttraumatic inflammation and apoptosis was significantly reduced after NPC transplantation and GF administration. Our data suggest that NPC transplantation is feasible with the use of only EGF, bFGF, and PDGF-AA as supporting growth factors.


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