Mesenchymal stem cells in radiation-induced lung injury: From mechanisms to therapeutic potential

Abstract

Radiotherapy (RT) is an effective treatment option for multiple thoracic malignant tumors, including lung cancers, thymic cancers, and tracheal cancers. Radiation-induced lung injury (RILI) is a serious complication of radiotherapy. Radiation causes damage to the pulmonary cells and tissues. Multiple factors contribute to the progression of Radiation-induced lung injury, including genetic alterations, oxidative stress, and inflammatory responses. Especially, radiation sources contribute to oxidative stress occurrence by direct excitation and ionization of water molecules, which leads to the decomposition of water molecules and the generation of reactive oxygen species (ROS), reactive nitrogen species (RNS). Subsequently, reactive oxygen species and reactive nitrogen species overproduction can induce oxidative DNA damage. Immune cells and multiple signaling molecules play a major role in the entire process. Mesenchymal stem cells (MSCs) are pluripotent stem cells with multiple differentiation potentials, which are under investigation to treat radiation-induced lung injury. Mesenchymal stem cells can protect normal pulmonary cells from injury by targeting multiple signaling molecules to regulate immune cells and to control balance between antioxidants and prooxidants, thereby inhibiting inflammation and fibrosis. Genetically modified mesenchymal stem cells can improve the natural function of mesenchymal stem cells, including cellular survival, tissue regeneration, and homing. These reprogrammed mesenchymal stem cells can produce the desired products, including cytokines, receptors, and enzymes, which can contribute to further advances in the therapeutic application of mesenchymal stem cells. Here, we review the molecular mechanisms of radiation-induced lung injury and discuss the potential of Mesenchymal stem cells for the prevention and treatment of radiation-induced lung injury. Clarification of these key issues will make mesenchymal stem cells a more fantastic novel therapeutic strategy for radiation-induced lung injury in clinics, and the readers can have a comprehensive understanding in this fields.

Keywords: cytokines; gene modification; inflammatory response; mesenchymal stem cells (MSCs); oxidative stress; radiation-induced lung injury (RILI).