The potential of mesenchymal stem cells in the management of radiation enteropathy

Abstract

Although radiotherapy is effective in managing abdominal and pelvic malignant tumors, radiation enteropathy is still unavoidable. This disease severely affects the quality of life of cancer patients due to some refractory lesions, such as intestinal ischemia, mucositis, ulcer, necrosis or even perforation. Current drugs or prevailing therapies are committed to alleviating the symptoms induced by above lesions. But the efficacies achieved by these interventions are still not satisfactory, because the milieus for tissue regeneration are not distinctly improved. In recent years, regenerative therapy for radiation enteropathy by using mesenchymal stem cells is of public interests. Relevant results of preclinical and clinical studies suggest that this regenerative therapy will become an attractive tool in managing radiation enteropathy, because mesenchymal stem cells exhibit their pro-regenerative potentials for healing the injuries in both epithelium and endothelium, minimizing inflammation and protecting irradiated intestine against fibrogenesis through activating intrinsic repair actions. In spite of these encouraging results, whether mesenchymal stem cells promote tumor growth is still an issue of debate. On this basis, we will discuss the advances in anticancer therapy by using mesenchymal stem cells in this review after analyzing the pathogenesis of radiation enteropathy, introducing the advances in managing radiation enteropathy using regenerative therapy and exploring the putative actions by which mesenchymal stem cells repair intestinal injuries. At last, insights gained from the potential risks of mesenchymal stem cell-based therapy for radiation enteropathy patients may provide clinicians with an improved awareness in carrying out their studies.

Figure 1

The structure of villus-crypt axis. This figure shows the homeostasis of intestinal epithelium regulating by CBC stem cells

Figure 2

The pathogenesis of radiation enteropathy. Four events are involved in the pathogenesis of radiation enteropathy, including de-epithelization, ischemia, oxidative stress and fibrogenesis

Figure 3

The contribution of neuroimmune interactions to RE development. Upon being irradiated, the mast cells will be activated, presenting the release of pro-inflammatory and pro-fibrotic effectors, including TNF-α, histamine, LT, IL-4 and TGF-β1. These actions will be amplified by substance P, whereas be reversed by CGRP. LT, leukotriene; CGRP, calcitonin gene-related peptide

Figure 4

The putative actions by which MSCs repair radiation enteropathy. Four steps are involved in the processes of MSCs healing injuries in irradiated intestine, including cell-homing, interacting with immune cells, boosting intrinsic repair actions and reversing the homeostasis of injured tissue

Figure 5

The interactions between MSCs and immune cells/Bacteria. Upon co-culturing with MSCs, the pro-inflammatory profiles of immune cells, including macrophages, dendritic cells, T effector cells, NK cells and mast cells, will be altered into the anti-inflammatory ones. By contrast, the proliferation of Tregs will be promoted by MSCs. Besides, MSCs have the anti-bacterial potentials, and the phagocytosis by neutrophils and macrophages will be strengthened by MSCs