Secretome from hypoxia-conditioned adipose-derived mesenchymal stem cells promotes the healing of gastric mucosal injury in a rodent model.
Biochim Biophys Acta Mol Basis Dis
; 1864(1): 178-188, 2018 Jan.
Article
en En
| MEDLINE
| ID: mdl-28993190
ABSTRACT
Studies 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% O2 and 5% O2 for 48h. 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-PGE2 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-PGE2 axis with a paracrine activity involving CCL-20 factor.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Gastropatías
/
Cicatrización de Heridas
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Medios de Cultivo Condicionados
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Proteoma
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Células Madre Mesenquimatosas
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Mucosa Gástrica
Tipo de estudio:
Prognostic_studies
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Biochim Biophys Acta Mol Basis Dis
Año:
2018
Tipo del documento:
Article
País de afiliación:
Hong Kong