Abstract
Radiation-induced enteropathy remains a major complication after accidental or therapeutic exposure to ionizing radiation. Recent evidence suggests that intestinal microvascular damage significantly affects the development of radiation enteropathy. Mesenchymal stem cell (MSC) therapy is a promising tool to regenerate various tissues, including skin and intestine. Further, photobiomodulation (PBM), or low-level light therapy, can accelerate wound healing, especially by stimulating angiogenesis, and stem cells are particularly susceptible to PBM. Here, we explored the effect of PBM on the therapeutic potential of MSCs for the management of radiation enteropathy. In vitro, using human umbilical cord blood-derived MSCs, PBM increased proliferation and self-renewal. Intriguingly, the conditioned medium from MSCs treated with PBM attenuated irradiation-induced apoptosis and impaired tube formation in vascular endothelial cells, and these protective effects were associated with the upregulation of several angiogenic factors. In a mouse model of radiation-induced enteropathy, treatment with PBM-preconditioned MSCs alleviated mucosal destruction, improved crypt cell proliferation and epithelial barrier functions, and significantly attenuated the loss of microvascular endothelial cells in the irradiated intestinal mucosa. This treatment also significantly increased angiogenesis in the lamina propria. Together, we suggest that PBM enhances the angiogenic potential of MSCs, leading to improved therapeutic efficacy for the treatment of radiation-induced enteropathy.
Highlights
The intestine is one of the most vulnerable organs to radiation toxicity due to its rapid proliferation [1]
To assess whether PBM affects Mesenchymal stem cell (MSC) proliferation and to determine the dose required for maximal enhancement of MSC ability, we used variable fluences
A number of preclinical studies have encouraged the application of MSC-based therapies to repair intestinal radiation-induced damage
Summary
The intestine is one of the most vulnerable organs to radiation toxicity due to its rapid proliferation [1]. The contemporary understanding of the pathogenesis of radiation-induced enteropathy is far more complex, and involves interactions among multiple cell compartments including epithelial, mesenchymal, and vascular endothelial cells, as well as the immune system, the enteric nervous system, and the gut microbiome [2]. Among these cell populations, considerable evidence has indicated that the endothelium plays a central role in normal tissue injury induced by radiation exposure. The prevention of radiation-induced endothelial damage attenuates crypt cell loss and dysfunction, organ failure, and death [8,9,10,11]
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