scholarly journals Intraventricular injections of mesenchymal stem cells activate endogenous functional remyelination in a chronic demyelinating murine model

2016 ◽  
Vol 7 (5) ◽  
pp. e2223-e2223 ◽  
Author(s):  
P Cruz-Martinez ◽  
S González-Granero ◽  
M M Molina-Navarro ◽  
J Pacheco-Torres ◽  
J M García-Verdugo ◽  
...  

Abstract Current treatments for demyelinating diseases are generally only capable of ameliorating the symptoms, with little to no effect in decreasing myelin loss nor promoting functional recovery. Mesenchymal stem cells (MSCs) have been shown by many researchers to be a potential therapeutic tool in treating various neurodegenerative diseases, including demyelinating disorders. However, in the majority of the cases, the effect was only observed locally, in the area surrounding the graft. Thus, in order to achieve general remyelination in various brain structures simultaneously, bone marrow-derived MSCs were transplanted into the lateral ventricles (LVs) of the cuprizone murine model. In this manner, the cells may secrete soluble factors into the cerebrospinal fluid (CSF) and boost the endogenous oligodendrogenic potential of the subventricular zone (SVZ). As a result, oligodendrocyte progenitor cells (OPCs) were recruited within the corpus callosum (CC) over time, correlating with an increased myelin content. Electrophysiological studies, together with electron microscopy (EM) analysis, indicated that the newly formed myelin correctly enveloped the demyelinated axons and increased signal transduction through the CC. Moreover, increased neural stem progenitor cell (NSPC) proliferation was observed in the SVZ, possibly due to the tropic factors released by the MSCs. In conclusion, the findings of this study revealed that intraventricular injections of MSCs is a feasible method to elicit a paracrine effect in the oligodendrogenic niche of the SVZ, which is prone to respond to the factors secreted into the CSF and therefore promoting oligodendrogenesis and functional remyelination.

2017 ◽  
Vol 8 (5) ◽  
pp. e2809-e2809
Author(s):  
Pablo Cruz-Martinez ◽  
Susana González-Granero ◽  
María Micaela Molina-Navarro ◽  
Jesus Pacheco-Torres ◽  
Jose Manuel García-Verdugo ◽  
...  

2010 ◽  
Vol 79 (5) ◽  
pp. 317 ◽  
Author(s):  
Yong Beom Cho ◽  
Min Shik Kim ◽  
Min Jeong Kang ◽  
Hee Jung Shin ◽  
Seok-Hyung Kim ◽  
...  

2019 ◽  
Vol 60 (3) ◽  
pp. 328-335 ◽  
Author(s):  
Adrien Bouglé ◽  
Pierre Rocheteau ◽  
David Briand ◽  
David Hardy ◽  
Franck Verdonk ◽  
...  

2015 ◽  
Vol 37 (1) ◽  
pp. 321-330 ◽  
Author(s):  
Zhen Liu ◽  
Cunfu Wang ◽  
Xiao Wang ◽  
Shunliang Xu

Background/Aims: Alzheimer's disease (AD) is one of the most common dementias among aged people, and is clinically characterized by progressive memory loss, behavioral and learning dysfunction and cognitive deficits. So far, this is no cure for AD. A therapeutic effect of transplantation of mesenchymal stem cells (MSCs) into murine model of AD has been reported, but remains to be further improved. Brn-4 is a transcription factor that plays a critical role in neuronal development, whereas the effects of Brn-4 overexpression in transplanted MSCs on AD are unknown. Methods: MSCs were isolated from mouse bone marrow and induced to overexpress antisense of miRNA-937 (as-miR-937) through adeno-associated virus (AAV)-mediated transduction, and purified by flow cytometry based on expression of a GFP co-transgene in the cells. The Brn-4 levels in mouse MSCs were examined in miR-937-modified MSCs by RT-qPCR and by Western blot. These miR-937-modified MSCs were then transplanted into an APP/PS1 transgenic AD model in mice. The effects of saline control, MSCs and asmiR-937 MSCs on AD mice were examined by deposition of amyloid-beta peptide aggregates (Aβ), social recognition test (SR), Plus-Maze Discriminative Avoidance Task (PM-DAT) and the levels of Brain-derived neurotrophic factor (BDNF) in the mouse brain. Results: MSCs expressed high levels of Brn-4 transcripts but low levels of Brn-4 protein. Poor protein vs mRNA levels of Brn-4 in MSCs appeared to result from the presence of high levels of miR-937 in MSCs. miR-937 inhibited translation of Brn-4 mRNA through binding to the 3'-UTR of the Brn-4 mRNA in MSCs. Expression of as-miR-937 significantly increased Brn-4 protein levels in MSCs. Transplantation of as-miR-937-expressing MSCs significantly reduced the deposition of Aβ, increased the levels of BDNF, and significantly improved the appearance in SR and PM-DAT in AD mice. Conclusion: Overexpression of as-miR-937 in MSCs may substantially improve the therapeutic effects of MSCs on AD, possibly through augmenting Brn-4 levels in MSCs.


2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Hakan Orbay ◽  
Morikuni Tobita ◽  
Hiroshi Mizuno

Mesenchymal stem cells (MSCs) are adult stem cells that were initially isolated from bone marrow. However, subsequent research has shown that other adult tissues also contain MSCs. MSCs originate from mesenchyme, which is embryonic tissue derived from the mesoderm. These cells actively proliferate, giving rise to new cells in some tissues, but remain quiescent in others. MSCs are capable of differentiating into multiple cell types including adipocytes, chondrocytes, osteocytes, and cardiomyocytes. Isolation and induction of these cells could provide a new therapeutic tool for replacing damaged or lost adult tissues. However, the biological properties and use of stem cells in a clinical setting must be well established before significant clinical benefits are obtained. This paper summarizes data on the biological properties of MSCs and discusses current and potential clinical applications.


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