Department of Endocrinology, the Affiliated Drum Tower Hospital of Nanjing University Medical School, No. 321, Zhongshan Road, Nanjing, 210008, China.
School of Clinical Medicine and Nursing, Suzhou Vocational Health College, Jiangsu, China.
Sci Rep. 2016 Dec 1;6:37894. doi: 10.1038/srep37894.
Mesenchymal stem cells (MSCs) transplantation is a promising therapeutic strategy for type 1 diabetes (T1D). However, little is known on whether MSC transplantation can benefit T1D patients with ketoacidosis and its potential actions. Here, we show that infusion with bone marrow MSCs preserves β-cell function in some T1D patients with ketoacidosis by decreasing exogenous insulin requirement and increasing plasma C-peptide levels up to 1-2 years. MSC transplantation increased plasma and islet insulin contents in non-obese diabetic (NOD) mice with severe diabetes. In comparison with severe diabetes controls, MSC infusion reduced insulitis, decreased pancreatic TNF-α, and increased IL-10 and TGF-β1 expression in NOD mice. MSC infusion increased the percentages of splenic Tregs and levels of plasma IL-4, IL-10 and TGF-β1, but reduced the percentages of splenic CD8 T and levels of plasma IFN-γ, TNF-α and IL-17A in NOD mice. Finally, infused MSCs predominantly accumulated in pancreatic tissues at 28 days post infusion. The effects of MSCs on preserving β-cell function and modulating inflammation tended to be dose-dependent and multiple doses of MSCs held longer effects in NOD mice. Hence, MSC transplantation preserved β-cell function in T1D patients and NOD mice with severe diabetes by enhancing Treg responses.
间充质干细胞（MSCs）移植是治疗 1 型糖尿病（T1D）的一种有前途的治疗策略。然而，对于 MSCs 移植是否能使酮症酸中毒的 T1D 患者受益及其潜在作用，目前知之甚少。在这里，我们发现骨髓 MSCs 输注通过减少外源性胰岛素需求并将血浆 C 肽水平提高至 1-2 年，可维持一些酮症酸中毒 T1D 患者的β细胞功能。MSC 移植增加了非肥胖型糖尿病（NOD）小鼠严重糖尿病模型中血浆和胰岛胰岛素含量。与严重糖尿病对照组相比，MSC 输注可减少胰岛炎，降低胰腺 TNF-α，并增加 NOD 小鼠中 IL-10 和 TGF-β1 的表达。MSC 输注可增加脾 Tregs 的百分比和血浆中 IL-4、IL-10 和 TGF-β1 的水平，但可降低脾 CD8 T 的百分比和血浆 IFN-γ、TNF-α 和 IL-17A 的水平。最后，输注的 MSCs 在输注后 28 天主要积聚在胰腺组织中。MSC 对保存β细胞功能和调节炎症的作用倾向于呈剂量依赖性，并且在 NOD 小鼠中多次 MSCs 输注的效果更持久。因此，MSC 移植通过增强 Treg 反应，可在 T1D 患者和严重糖尿病的 NOD 小鼠中保存β细胞功能。
