Treatment of chemically induced oral ulcer using adipose‐derived mesenchymal stem cell sheet

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Oral ulceration is a discontinuity or break in mucosa of oral cavity and can occur due to various etiologies, including trauma, dentures, dehydration, and viral or autoimmune diseases. Oral ulceration is a frequently encountered side effect, as a form of oral mucositis, in patients receiving radiation therapy with or without chemotherapy for head and neck cancer 1. Because the oral cavity plays an essential role in many key bodily functions, including nutrition (chewing and swallowing), breathing, and speaking, oral ulceration can have harmful effects on the nutritional intake, communication, daily activities, and quality of life of patients undergoing head and neck cancer treatment. In patients with head and neck cancer, current treatment strategies for oral mucositis, including ulceration, focus primarily on symptomatic measures, such as pain relief, support of nutritional intake, and improvement of oral hygiene, and on local therapy, including artificial saliva or hydrating gels to alleviate dryness and steroid injection of focal lesions 4. In addition to basic oral care, several agents, such as growth factors, cytokines, anti‐inflammatory agents, coating agents, natural agents, laser therapy, and cryotherapy, are recommended for management of oral mucositis secondary to cancer therapy 6.
Regenerative therapies using tissue stem cells have recently been tested. In particular, the effectiveness of cell therapy using mesenchymal stem cells (MSCs) has been demonstrated for regeneration of various tissues 11 and for healing of skin and mucosal wounds through cell differentiation or release of paracrine factors 13. MSCs can differentiate into multiple cell types and display paracrine functions, such as suppressing cell apoptosis, promoting angiogenesis, and activating stem cells at injured sites 15. In addition, transplanted MSCs have been shown to inhibit TGF‐β‐induced apoptosis and suppress activation of the NF‐κB signaling pathway at injured sites 18. Therefore, exogenous MSCs may accelerate the healing process and suppress formation of oral ulcers. This study assessed the regenerative capacity of MSCs that were directly transplanted using tissue‐engineered cell sheets on chemically induced oral ulceration. This research is a prerequisite step for future clinical trials aimed at developing cell‐based therapies for radiation or chemotherapy‐induced oral mucositis.
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