人牙龈间充质干细胞通过减少滤泡B细胞比例预防非肥胖糖尿病小鼠糖尿病

Human Gingival Stem Cells Prevent Diabetes in NOD Mice by Reducing Follicular B Cells

【目的】1型糖尿病是由于慢性免疫炎症破坏了胰岛β细胞,导致血糖升高。间充质干细胞可以预防及治疗糖尿病及其并发症的发生,然而对牙龈间充质干细胞(GMSCs)预防糖尿病的效果和潜在机制知之甚少。本研究旨在研究GMSCs在预防小鼠1型糖尿病的机制,寻找临床治疗糖尿病的靶点。【方法】我们将人GMSCs注射到NOD小鼠体内,观察血糖的变化趋势,通过免疫组化染色观察胰岛β细胞的存活情况,并通过流式分析检测小鼠脾脏中T细胞、B细胞及巨噬细胞的比例变化。最后,将NOD小鼠脾脏淋巴细胞回输至NOD-SCID小鼠,观察NOD-SCID小鼠的血糖水平及糖尿病发病率。【结果】GMSCs明显降低了NOD小鼠的糖尿病发病率,对照组小鼠在27周龄时有64%患糖尿病,而GMSC组只有35%,P=0.013。GMSCs处理的小鼠脾脏中滤泡B细胞比例从(52.2±4.1)%下降到(43.2±5.3)%,P=0.008,而其他类型的免疫细胞没有明显变化。免疫组化结果显示,GMSCs可以有效地提高胰岛β细胞的存活率,使其能够持续产生胰岛素以控制血糖。最后,我们发现患病小鼠脾脏淋巴细胞回输治疗能够促进NOD-SCID小鼠糖尿病的发生。【结论】GMSCs可以通过减少脾脏中的滤泡B细胞比例来预防NOD小鼠的糖尿病发生。

【Background】Type 1 diabetes is caused by a chronic immune response that destroys islet beta cells,re‐sulting in elevated blood glucose.Mesenchymal stem cells can prevent and treat the development of diabetes and its compli‐cations.However,little is known about the effects and potential mechanisms of Gingival mesenchymal stem cells(GMSCs)in preventing diabetes.The aim of this study is to investigate the mechanism of GMSCs in preventing type 1 diabetes in mice and to find targets for clinical treatment of diabetes.【Methods】We injected human GMSCs into NOD mice to observe the trend of blood glucose,observed the survival of pancreaticβ-cells by immunohistochemistry,and detected the change of immune cells in the spleen of mice by flow analysis.Finally,the immune cells in NOD mice were transfused into NOD-SCID mice to observe the onset of diabetes in NOD-SCID mice.【Results】GMSCs significantly reduced the incidence of di‐abetes in NOD mice,with 64%of control mice developing diabetes at 27 weeks of age compared with 35%in the GMSC group,P=0.013.The percentage of Follicular B cells(FO B cell)in the spleen of GMSCs-treated mice decreased from(52.2±4.1)%to(43.2±5.3)%,P=0.008,while other types of immune cells did not change significantly.The immunohisto‐chemical results showed that GMSCs could effectively improve the survival of pancreaticβ-cells,which could continuous‐ly produce insulin to control blood glucose.Finally,we found the spleen cells transfusion could prevent the development of diabetes in NOD-SCID mice.【Conclusion】GMSCs can reduce diabetes in mice by reducing FO B cells in the spleen.