Journal
STEM CELL RESEARCH & THERAPY
Volume 6, Issue -, Pages -Publisher
BMC
DOI: 10.1186/s13287-015-0245-4
Keywords
Mesenchymal stem cells; Autophagy; Apoptosis; Sepsis; Bcl-2
Funding
- Ministry of Science and Technology of China [2011CB966200]
- National Natural Science Foundation of China [81400297, 81370303]
Ask authors/readers for more resources
Background: Mesenchymal stem cells (MSCs) have been widely applied to treat various inflammatory diseases. Inflammatory cytokines can induce both apoptosis and autophagy in MSCs. However, whether autophagy plays a pro-or con-apoptosis effect on MSCs in an inflammatory microenvironment has not been clarified. Methods: We inhibited autophagy by constructing MSCs with lentivirus containing small hairpin RNA to knockdown Beclin-1 and applied these MSCs to a model of sepsis to evaluate therapeutic effect of MSCs. Results: Here we show that inhibition of autophagy in MSCs increases the survival rate of septic mice more than control MSCs, and autophagy promotes apoptosis of MSCs during application to septic mice. Further study demonstrated that autophagy aggravated tumor necrosis factor alpha plus interferon gamma-induced apoptosis of MSCs. Mechanically, autophagy inhibits the expression of the pro-survival gene Bcl-2 via suppressing reactive oxygen species/mitogen-activated protein kinase 1/3 pathway. Conclusions: Our findings indicate that an inflammatory microenvironment-induced autophagy promotes apoptosis of MSCs. Therefore, modulation of autophagy in MSCs would provide a novel approach to improve MSC survival during immunotherapy.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available