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Cell Journal، جلد ۱۶، شماره Suppl ۱، صفحات ۱۳۹-۱۳۹
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عنوان انگلیسی Ps-108: Autophagy Modulation: A Key to Mesenchymal Stem Cell Survival Following Liver Cell Transplantation
چکیده انگلیسی مقاله Objective: Therapeutic applications of bone marrow mesenchymal stem cells (BMCSs) as regenerative medicine "magic bullets" are limited due to their early death within the first few days following transplantation. This challenge resulted in development of several strategies to reinforce MSCs against lethal factors. In this study, we introduce a new strategy such as modulation of autophagy, a garbage disposal system in cell biology. We evaluated the effects of autophagy modulation in MSCs survival after transplantation to acute liver failure model in mice. Materials and Methods: MSCs were isolated from discarded BM transplantation collection bags and filters. Autophagy was induced in MSCs by rapamycin. On the other hand, autophagy was inhibited through shRNA knockdown of ATG7 as autophagy crucial gene following cloning in DH5α E.coli. Induction or inhibition of autophagy was evaluated by GFP-LC3 puncta counting, western blotting and immunocytochemistry. In the in vitro phase, the response of MSCs following inhibition or induction of autophagy against lethal conditions were determined in terms of survival. Multilineage differentiation capacity of these MSCs were also evaluated. Then, in the in vivo phase, control and MSCs with inhibited or induced autophagy were transplanted to mice in which liver injured through CCl4 injection to determine whether modulations of autophagy would affect on repair. Finally, pathological and biochemical assays were performed to evaluate the regenerative potential of these MSCs. Results: Autophagy inhibition increased survival of MSCs against unfavorable microenvironments such as hypoxia, serum depriviation and oxidative stress conditions. Moreover, inhibition of autophagy resulted in better recovery of injured liver. Interestingly, autophagy modulation had no adverse effect on MSCs multilineage differentiation potential. Conclusion: Modulation of autophagy might act as a new strategy to improve the efficacy of MSC-based cell therapy at least in Liver injury.
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نشانی اینترنتی http://celljournal.org/journal/article/abstract/433
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