Applications and therapeutic mechanisms of action of mesenchymal stem cells in radiation-induced lung injury

Abstract

Radiation-induced lung injury (RILI) is one of the most common complications associated with radiotherapy, characterized by early-stage radiation pneumonia and subsequent radiation pulmonary fibrosis. However, effective therapeutic strategies for RILI are currently lacking. Recently, an increasing number of studies reported that mesenchymal stem cells (MSCs) can enhance the regeneration of damaged tissue, modulate the inflammatory response, reduce the levels of fibrotic cytokines and reactive oxygen species, and inhibit epithelial-mesenchymal transformation. Interestingly, MSCs can also exert immunosuppressive effects, which highlights a new potential therapeutic activity of MSCs for managing RILI. Here, we reviewed the potential applications and therapeutic mechanisms of action of MSCs in RILI, which will represent a good compendium of information for researchers in this field.

Keywords: Mesenchymal stem cell; Radiation-induced lung injury; Stem cell therapy.

Fig. 1

The primary mechanisms /pathogenesis of radiation-induced lung injury (RILI): direct DNA damage; the generation of ROS; RAAS system activation; the activation of the immune system. ROS, reactive oxygen species; RAAS system, renin-angiotensin-aldosterone system; EMT, epithelial-to-mesenchymal transition

Fig. 2

Molecular mechanisms of MSC-based therapy for RILI through the following aspects: reduction of inflammatory and fibrosis reaction; resistance of oxidative stress; inhibition of EMT; immunosuppressive properties; release of extracellular vesicles. EMT, epithelial-to-mesenchymal transition; IL-1β, interleukin 1β; IL-6, interleukin 6; IL-10, interleukin 10; TNF-α, tumor necrosis factor α; SOD1, superoxide dismutase 1; SOD3, superoxide dismutase 3; MnSOD, manganese superoxide dismutase; HGF, hematopoietic growth factor; EVs, extracellular vesicles; PGE2, prostaglandin E2; IDO, indoleamine 2,3-dioxygenase