Beckman Laser Institute Korea, Dankook University College of Medicine, Cheonan, Republic of Korea.
Medical Laser Research Center, Dankook University College of Medicine, Cheonan, Republic of Korea.
Stem Cell Res Ther. 2024 Apr 8;15(1):103. doi: 10.1186/s13287-024-03694-4.
Oral ulcers are a common side effect of chemotherapy and affect patients' quality of life. While stem cell transplantation is a potential treatment for oral ulcers, its efficacy is limited as the stem cells tend to remain in the affected area for a short time. This study aims to develop a treatment for oral ulcers by using trimethyl chitosan (TMC) hydrogel with human tonsil-derived stem cells (hTMSCs) to increase the therapeutic effect of stem cells and investigate their effectiveness.
Animals were divided into four experimental groups: Control, TMC hydrogel, hTMSCs, and hTMSCs loaded in TMC hydrogel (Hydrogel + hTMSCs) (each n = 8). Oral ulcers were chemically induced by anesthetizing the rats followed by injection of dilute acetic acid in the right buccal mucosa. After confirming the presence of oral ulcers in the animals, a single subcutaneous injection of 100 µL of each treatment was applied to the ulcer area. Histological analyses were performed to measure inflammatory cells, oral mucosal thickness, and fibrosis levels. The expression level of inflammatory cytokines was also measured using RT-PCR to gauge therapeutic the effect.
The ulcer size was significantly reduced in the TMC hydrogel + hTMSCs group compared to the control group. The stem cells in the tissue were only observed until Day 3 in the hTMSCs treated group, while the injected stem cells in the TMC Hydrogel + hTMSCs group were still present until day 7. Cytokine analysis related to the inflammatory response in the tissue confirmed that the TMC Hydrogel + hTMSCs treated group demonstrated superior wound healing compared to other experimental groups.
This study has shown that the adhesion and viability of current stem cell therapies can be resolved by utilizing a hydrogel prepared with TMC and combining it with hTMSCs. The combined treatment can promote rapid healing of oral cavity wounds by enhancing anti-inflammatory effects and expediting wound healing. Therefore, hTMSC loaded in TMC hydrogel was the most effective wound-healing approach among all four treatment groups prolonging stem cell survival. However, further research is necessary to minimize the initial inflammatory response of biomaterials and assess the safety and long-term effects for potential clinical applications.
口腔溃疡是化疗的常见副作用，会影响患者的生活质量。虽然干细胞移植是治疗口腔溃疡的一种潜在方法，但由于干细胞在受影响区域停留的时间很短，其疗效有限。本研究旨在通过使用壳聚糖（TMC）水凝胶和人扁桃体来源的干细胞（hTMSCs）来治疗口腔溃疡，以增加干细胞的治疗效果并研究其疗效。
动物分为四个实验组：对照组、TMC 水凝胶组、hTMSCs 组和负载于 TMC 水凝胶中的 hTMSCs 组（每组 n=8）。通过麻醉大鼠并在右侧颊黏膜注射稀醋酸化学诱导口腔溃疡。在动物出现口腔溃疡后，将每种治疗方法的 100 µL 单次皮下注射到溃疡区域。进行组织学分析以测量炎症细胞、口腔黏膜厚度和纤维化水平。还使用 RT-PCR 测量炎症细胞因子的表达水平，以评估治疗效果。
与对照组相比，TMC 水凝胶+hTMSCs 组的溃疡面积显著减小。在 hTMSCs 处理组中，组织中的干细胞仅在第 3 天观察到，而在 TMC 水凝胶+hTMSCs 组中注射的干细胞仍存在至第 7 天。组织中与炎症反应相关的细胞因子分析证实，TMC 水凝胶+hTMSCs 处理组的伤口愈合效果优于其他实验组。
本研究表明，通过利用 TMC 制备的水凝胶结合 hTMSCs，可以解决当前干细胞疗法的黏附性和活力问题。联合治疗可以通过增强抗炎作用和加速伤口愈合来促进口腔伤口的快速愈合。因此，负载于 TMC 水凝胶中的 hTMSC 是所有四种治疗组中最有效的伤口愈合方法，可延长干细胞的存活时间。然而，为了实现潜在的临床应用，还需要进一步研究以最小化生物材料的初始炎症反应，并评估其安全性和长期效果。
