hESC-derived mesenchymal stem cells Promote Oral Mucositis Healing via the PI3K/AKT Pathway

Abstract

Abstract Objective Oral mucositis (OM) is among the most pervasive adverse reactions caused by radiotherapy or chemotherapy during cancer treatment. This study focused on the reparative effects of human embryonic stem cell-derived mesenchymal stem cells (hESC-MSCs) in OM and possible mechanisms. Materials and Methods An ulcer model was created in the rat buccal mucosa to simulate OM, and hESC-MSCs were injected 48h later to assess their reparative effects. The efficacy of hESC-MSCs in regulating apoptosis and proliferation in LPS- or 5-FU-injured HaCaT cells was studied in vitro using a transwell coculture system. Subsequently, the PI3K inhibitor LY24002 was used to assess whether hESC-MSCs regulated injured HaCaT cells through PI3K/AKT pathway. Results We found that hESC-MSCs injection promoted OM healing in rats through the acceleration of re-epithelialization, and a decrease in apoptosis. Our findings also revealed that the hESC-MSCs treatment led to a reduction in the quantity of HaCaT cells undergoing apoptosis. Western blot analysis revealed that hESC-MSCs activated AKT, resulting in increased protein levels of PCNA and BCL-2, decreased protein levels of Bax and Caspase-3. Whereas, LY294002 reversed these changes. Conclusions hESC-MSCs promoted OM healing, inhibited LPS- or 5-FU-injured HaCaT cell apoptosis, and increased their proliferation via the PI3K/AKT pathway.