scholarly journals Genetically Modified Mesenchymal Stem Cells: The Next Generation of Stem Cell-Based Therapy for TBI

2020 ◽  
Vol 21 (11) ◽  
pp. 4051
Author(s):  
Rami Ahmad Shahror ◽  
Chung-Che Wu ◽  
Yung-Hsiao Chiang ◽  
Kai-Yun Chen

Mesenchymal stem cells (MSCs) are emerging as an attractive approach for restorative medicine in central nervous system (CNS) diseases and injuries, such as traumatic brain injury (TBI), due to their relatively easy derivation and therapeutic effect following transplantation. However, the long-term survival of the grafted cells and therapeutic efficacy need improvement. Here, we review the recent application of MSCs in TBI treatment in preclinical models. We discuss the genetic modification approaches designed to enhance the therapeutic potency of MSCs for TBI treatment by improving their survival after transplantation, enhancing their homing abilities and overexpressing neuroprotective and neuroregenerative factors. We highlight the latest preclinical studies that have used genetically modified MSCs for TBI treatment. The recent developments in MSCs’ biology and potential TBI therapeutic targets may sufficiently improve the genetic modification strategies for MSCs, potentially bringing effective MSC-based therapies for TBI treatment in humans.

2018 ◽  
Vol 7 (11) ◽  
pp. e1509821 ◽  
Author(s):  
Eliza Kwiatkowska-Borowczyk ◽  
Patrycja Czerwińska ◽  
Jacek Mackiewicz ◽  
Katarzyna Gryska ◽  
Urszula Kazimierczak ◽  
...  

2010 ◽  
Vol 79 (3) ◽  
pp. 182-193 ◽  
Author(s):  
Rebekka K. Schneider ◽  
Andrea Püllen ◽  
Rafael Kramann ◽  
Jörg Bornemann ◽  
Ruth Knüchel ◽  
...  

2017 ◽  
Vol 2017 ◽  
pp. 1-11
Author(s):  
Weifeng Lu ◽  
Xiaoli Chen ◽  
Yi Si ◽  
Shichai Hong ◽  
Zhengyu Shi ◽  
...  

Mesenchymal stem cells (MSCs) have been increasingly tested in cell-based therapy to treat numerous diseases. Genetic modification to improve MSC behavior may enhance posttransplantation outcome. This study aims to test the potential therapeutic benefits of rat bone marrow MSCs overexpressing hypoxia-inducible factor 2α (rMSCsHIF-2α) in a rat hindlimb ischemia model. PBS, rMSCs, or rMSCsHIF-2α were injected into rat ischemic hindlimb. Compared with the injection of PBS or rMSCs, transplantation of rMSCsHIF-2α significantly improved blood perfusion, increased the number of vessel branches in the muscle of the ischemic hindlimb, and improved the foot mobility of the ischemic hindlimb (all P<0.05). rMSCHIF-2α transplantation also markedly increased the expression of proangiogenic factors VEGF, bFGF, and SDF1 and Notch signaling proteins including DII4, NICD, Hey1, and Hes1, whereas it reduced the expression of proapoptotic factor Bax in the muscle of the ischemic hindlimb. Overexpression of HIF-2α did not affect rMSC stemness and proliferation under normoxia but significantly increased rMSC migration and tube formation in matrigel under hypoxia (all P<0.05). RMSCsHIF-2α stimulated endothelial cell invasion under hypoxia significantly (P<0.05). Genetic modification of rMSCs via overexpression of HIF-2α improves posttransplantation outcomes in a rat hindlimb ischemia model possibly by stimulating proangiogenic growth factors and cytokines.


Cartilage ◽  
2020 ◽  
pp. 194760352094294
Author(s):  
Wei Ding ◽  
Yong-qing Xu ◽  
Ying Zhang ◽  
An-xu Li ◽  
Xiong Qiu ◽  
...  

Objective Osteoarthritis (OA) is a chronic joint disease characterized by degeneration of articular cartilage and secondary osteogenesis. Cell-based agents, such as mesenchymal stem cells, have turned into the most extensively explored new therapeutic agents for OA. However, evidence-based research is still lacking. Methods We searched public databases up to February 2020 and only included randomized controlled trials. The outcomes included the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), the Knee Injury and Osteoarthritis Outcome Score (KOOS), the visual analogue scale (VAS) score, and serious adverse events (SAEs). A network meta-analysis was also performed in this work. Results We included 13 studies in the meta-analysis. The effect size showed that cell-based therapy did not significantly reduce the WOMAC score at the 6-month follow-up (standard mean difference [SMD] −3.6; 95% confidence interval [CI] −0.90 to 0.18; P = 0.1928). However, cell-based therapy significantly improved the KOOS at the 12-month follow-up (SMD 0.68; 95% CI 0.07-1.30; P = 0.0288) and relieved pain (SMD −1.05; 95% CI −1.46 to −0.64; P < 0.0001). The findings also indicated that high-dosage adipose-derived mesenchymal stem cells (ADMSCs) may be more advantageous in terms of long-term effects. Conclusions Cell-based therapy had a better effect on KOOS improvement and pain relief without safety concerns. However, cell-based therapy did not show a benefit in terms of the WOMAC. Allogeneic cells might have advantages compared to controls in the WOMAC and KOOS scores. The long-term effect of high-dose ADMSC treatment for OA is worthy of further study.


Author(s):  
N. V. Baranova ◽  
L. A. Kirsanova ◽  
Z. Z. Gonikova ◽  
A. S. Ponomareva ◽  
V. I. Sevastianov

Aim. To research the rat bone marrow mesenchymal stem cells (MSC BM) effect to the viability of isolated rat OL during cultivation with microstructured collagen-containing hydrogel (BMCH).Materials and methods. Rat islets and MSC BM were isolated according to  classical technique with some modifications. The experiments on the co- cultivation were carried out under standard conditions. Islet’s viability was  determined by immunofluorescence staining.Results. TheOL cultivation with BMCH and MSCBM resulted in destructive changes of isletson the third day, and complete destruction of OL was observed  on the seventh day. At the same time, OL cultured with BMCH remained viable for 14 days of incubation.Conclusion. Cultivation of OL with BMCH and MSC BM did not contribute to the  long-term survival of the islets. Thus, there was no positive effect of MSC BM on the viability of pancreatic islets.


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