Abstract
BackgroundRadiation enteropathy is a common complication in patients with abdominopelvic cancer, but no treatment has yet been established. Stem cell therapy may be a viable therapeutic option because intestinal stem cells are highly vulnerable to ionizing radiation (IR) and stem cell loss explains its intractability to general treatment. Here, we investigated either prophylactic or therapeutic efficacy of human placenta-derived mesenchymal stem cells (hPDSCs) against radiation enteropathy and could identify biomarkers predicting a favorable response to stem cell therapy.MethodsWe challenged a radiation-induced enteropathy model with hPDSCs. After sacrifice, we checked the gross anatomy of small intestine, histology gross, and analyzed that, accompanied with molecular changes implicated in this model.ResultshPDSCs significantly improved the outcome of mice induced with either radiation enteropathy or lethal radiation syndrome (P < 0.01). hPDSCs exerted inhibitory actions on inflammatory cytokines, the re-establishment of epithelium homeostasis was completed with increasing endogenous restorative processes as assessed with increased levels of proliferative markers in the hPDSCs group, and a significant inhibition of IR-induced apoptosis. The preservation of cells expressing lysozyme, and Musashi-1 were significantly increased in the hPDSC treatment group. Both preventive and therapeutic efficacies of hPDSCs were noted against IR-induced enteropathy. Label-free quantification was used to identify biomarkers which predict favorable responses after hPDSC treatment, and finally glutathione S-transferase-mu type, interleukin-10, and peroxiredoxin-2 were validated as proteomic biomarkers predicting a favorable response to hPDSCs in radiation enteropathy.ConclusionshPDSCs may be a useful prophylactic and therapeutic cell therapy for radiation enteropathy.
Highlights
Radiation enteropathy is a common complication in patients with abdominopelvic cancer, but no treatment has yet been established
When mice were treated with human placenta-derived mesenchymal stem cells (hPDSCs), 1, 4, and 7 days after ionizing radiation (IR), there were either significant decreases in wet weights of small intestine (P < 0.001) or decreases in pathological scores assessed in jejunum or ileum, separately (P < 0.005, Fig. 1c)
On gross examination of liver surface color by group, a very pale color was noted in group 2 compared with group 3 (Fig. 1b, arrows), signifying that hPDSC administration maintained normal liver surface color in addition to the unchanged wet weights of small intestine compared to the control IR group (P < 0.001)
Summary
Radiation enteropathy is a common complication in patients with abdominopelvic cancer, but no treatment has yet been established. Stem cell therapy may be a viable therapeutic option because intestinal stem cells are highly vulnerable to ionizing radiation (IR) and stem cell loss explains its intractability to general treatment. Intestinal stem cells (SCs) and endothelial cells are especially radiosensitive, and it is common for them to be lost following IR. The loss of these cells can result in a disrupted mucosal barrier and insufficient blood supply to the gut [7, 8], and lead to troublesome radiation enteropathy. Patients may suffer from vomiting, diarrhea, abdominal pain, and bleeding [7], but no preventive or restorative treatment modalities are available
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