Secretome from hypoxia-conditioned adipose-derived mesenchymal stem cells promotes the healing of gastric mucosal injury in a rodent model
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AbstractStudies have indicated that the definitive engraftment and transdifferentiation potential of stem cells do not seem crucial for its property of tissue repair. Our previous study showed that transplantation of adipose-derived mesenchymal stem cells (ADMSCs) enhanced the healing of sutured gastric perforation. This study aimed to investigate the paracrine role of ADMSCs in the experimental gastric mucosal injury. Normoxia-conditioned medium (Nor CM) and hypoxia (HPO) CM were obtained after culturing ADMSCs in 20% O-2 and 5% O-2 for 48 h. Cell migration, proliferation, viability, and angiogenesis in vitro were significantly enhanced upon incubation with CM, especially the HPO CM. Experiments in vivo using a rodent model of gastric ulcer demonstrated that HPO CM treatment significantly accelerated wound healing by suppressing inflammation and promoting neovascularization and re-epithelization. Meanwhile, the infusion of HPO CM activated the COX2-PGE(2) axis both in vitro and in vivo. And the upregulation of COX2 was further dependent on the activation of ErK1/2-MAPK pathway. In addition, vascular endothelial growth factor, tissue inhibitors of metalloproteinases-1, and chemokine (C-C motif) ligand 20 (CCL-20) were analyzed as being highly abundant factors secreted by ADMSCs under hypoxic condition. Notably, the blockade of CCL-20 abrogated the HPO CM-induced COX2 signaling in the primary gastric mucosal epithelial cells, while incubation with recombinant CCL-20 increased the expression of COX2. In conclusion, the secretome from hypoxia-conditioned ADMSCs facilitates the repair of gastric mucosal injury through the enhancement of angiogenesis and re-epithelization, as well as the activation of COX2-PGE(2) axis with a paracrine activity involving CCL-20 factor.
All Author(s) ListXianfeng Xia, Philip Wai Yan Chiu, Ping Kuen Lam, Wai Ching Chin, Enders Kwok Wai Ng, James Yun Wong Lau
Journal nameBBA - Molecular Basis of Disease
Year2018
Month1
Volume Number1864
Issue Number1
PublisherElsevier
Pages178 - 188
ISSN0925-4439
eISSN0006-3002
LanguagesEnglish-United Kingdom
KeywordsAdipose-derived mesenchymal stem cells, Conditioned medium, Gastric mucosal injury, Hypoxia, Secretome

Last updated on 2020-04-04 at 11:45