Photobiomodulation Enhances the Angiogenic Effect of Mesenchymal Stem Cells to Mitigate Radiation-Induced Enteropathy

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.

The Effect of Photobiomodulation Therapy on the Differentiation, Proliferation, and Migration of the Mesenchymal Stem Cell: A Review

“…The study showed that low-level laser irradiation could increase angiogenesis by the inhibition of apoptosis in the mesenchymal stem. 4 The results from a study also showed that using an 808 nm laser could induce the neural differentiation of the umbilical cord MSCs to the neuron cells. The study also found that only an 808 nm laser could express the NeuN marker protein of neurons in 72 hours and a 635 nm laser increased the proliferation of the mesenchymal cells.…”

“…Photo-modulation is biologically attributed to light absorption by the internal photoreceptor of the respiratory chain in the mitochondria, which induces mitochondrial activation within cells. [3][4][5] At the cellular and molecular level, photons transmitted from a low-power laser can be absorbed by mitochondria, leading to an increase in the production of ATP. 6 It has been well-established that the bio-stimulatory effects of the laser are influenced by the following parameters: wavelength, energy density, power output, frequency/duration of irradiation, distance cells and laser spot/probe.…”

“…The purpose of this study was to summarize the results of the studies that have pointed toward the proliferation of these cells and their power of differentiation. 4 A lowpower laser has the potential to be effective in the biological function of the MSCs. Therefore, the application of lowlevel laser could be effective in accelerating bone fractures, wound healing, neuroregeneration, blood disorders, pain and inflammation, and dermatological treatments.…”

Irradiance plays a significant role in photobiomodulation of B16F10 melanoma cells by increasing reactive oxygen species and inhibiting mitochondrial function

“…of melanoma cells. Most of the blue light is used to inhibit cell proliferation and inactivate important wound pathogenic bacteria [9], while red light is used to promote cell proliferation, such as enhancing the angiogenic effect of mesenchymal stem cells [10] and could treat hair loss effectively [11]. Besides, PBM is non-invasive and does not cause much damage to the body like traditional therapy [12].…”

Current Concepts of Laser–Oral Tissue Interaction

“…Tissue-dependant extracellular effects of PBM may include the selective activation of anti-inflammatory cytokine pathways, resulting in the enhanced resolution of acute and chronic inflammation [ 22 ], an optimisation of the consequent production of regenerative products such as collagen and bone [ 23 , 24 , 25 , 26 ], improvements in lymphatic drainage, and an increase in the availability of O 2 to tissues consequent to vasodilatation and the ability to induce analgesia [ 27 ].…”