MSCs rescue impaired wound healing in a murine LAD1 model by adaptive responses to low TGF-β1 levels.

ABSTRACT: Mutations in the CD18 gene encoding the common β-chain of β2 integrins result in impaired wound healing in humans and mice suffering from leukocyte adhesion deficiency syndrome type 1 (LAD1). Transplantation of adipose tissue-derived mesenchymal stem cells (MSCs) restores normal healing of CD18^-/- wounds by restoring the decreased TGF-β1 concentrations. TGF-β1 released from MSCs leads to enhanced myofibroblast differentiation, wound contraction, and vessel formation. We uncover that MSCs are equipped with a sensing mechanism for TGF-β1 concentrations at wound sites. Low TGF-β1 concentrations as occurring in CD18^-/- wounds induce TGF-β1 release from MSCs, whereas high TGF-β1 concentrations suppress TGF-β1 production. This regulation depends on TGF-β receptor sensing an

SUBMITTER: Jiang D 

PROVIDER: S-EPMC7132342 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature