研究課題
We investigated effects and molecular mechanisms of mesenchymal stem cells (MSCs) on irradiated cells.Radiation-induced (8 Gy) human umbilical cord blood cell (HUVECs) death was inhibited by indirectly co-culturing human MSCs in trans-wells, presenting that MSCs may prevent HUVEC death via their producing humoral factors. First, we examined whether exosomes secreted from MSCs have inhibitory effects against radiation-induced cell death. Secreted exosomes clearly demonstrated the protection ability against irradiated cell death.Next, we examined the basic molecular mechanisms of cellular uptake of exosomes. Radiation increased cellular uptake of exosomes through increasing colocalization of CD29 and CD81 on cellular surfaces. Exosomes became incorporated into cells through selectively binding CD29/CD81 complex on cell surfaces. We also searched affected molecules revealing protection ability against radiation in exosomes. Several factors including anti-apoptotic proteins and micro RNAs, have been detected in exosomes of MSCs. Their functional analyses are under examination.We found that “a humoral factor A” secreted from MSCs inhibited radiation-induced intestinal epithelial cell death in vitro. Recombinant actor A inhibited radiation-induced epithelial cell death. Its knock-down with siRNA in MSCs lost the protection effects.Finally, we confirmed that the factor A was effective for intestinal injuries with lower body-irradiated model mouse. These results demonstrated that MSCs and their-derived factors are useful for regeneration of irradiated tissues.
すべて 2016 2015
すべて 雑誌論文 (2件) (うち査読あり 2件、 オープンアクセス 1件、 謝辞記載あり 1件)
Cell Tissue Res
巻: 0 ページ: 0
DOI 10.1007/s00441-016-2405-y
Eur J Haematol
巻: 10 ページ: 12536
