Infusion with Human Bone Marrow-derived Mesenchymal Stem Cells Improves β-cell Function in Patients and Non-obese Mice with Severe Diabetes.
Infusion with Human Bone Marrow-derived Mesenchymal Stem Cells Improves β-cell Function in Patients and Non-obese Mice with Severe Diabetes.
复制标题
输注人骨髓间充质干细胞可改善患有严重糖尿病的患者和非肥胖小鼠的 β 细胞功能
DOI：
10.1038/srep37894
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发表时间：
2016-12-01
影响因子：
4.6
通讯作者：
Zhu D
中科院分区：
文献类型：
--
作者：
Li L;Hui H;Jia X;Zhang J;Liu Y;Xu Q;Zhu D
骨髓间充质干细胞（MSCs）移植是治疗1型糖尿病（T1 D）的一种有前途的策略。然而，很少有人知道MSC移植是否可以使T1 D酮症酸中毒患者受益及其潜在的作用。在这里，我们表明，骨髓间充质干细胞输注通过减少外源性胰岛素需求和增加血浆C肽水平长达1-2年来保护某些酮症酸中毒T1 D患者的β细胞功能。骨髓间充质干细胞移植增加了严重糖尿病非肥胖糖尿病（NOD）小鼠的血浆和胰岛胰岛素含量。与严重糖尿病对照组相比，MSC输注减少了NOD小鼠的胰岛炎，降低了胰腺TNF-α，增加了IL-10和TGF-β1的表达。MSC输注可增加NOD小鼠脾脏T淋巴细胞百分比和血浆IL-4、IL-10、TGF-β1水平，降低脾脏CD 8 + T细胞百分比和血浆IFN-γ、TNF-α、IL-17 A水平。最后，输注后28天，输注的MSC主要积聚在胰腺组织中。MSC对保持β细胞功能和调节炎症的作用倾向于剂量依赖性，并且多剂量MSC在NOD小鼠中保持更长的作用。因此，MSC移植通过增强Treg应答在患有严重糖尿病的T1 D患者和NOD小鼠中保留了β细胞功能。
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.
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影响因子：
--
作者：
Gabr MM;Zakaria MM;Refaie AF;Khater SM;Ashamallah SA;Ismail AM;El-Halawani SM;Ghoneim MA
通讯作者：
Ghoneim MA
影响因子：
7.7
作者：
Jurewicz M;Yang S;Augello A;Godwin JG;Moore RF;Azzi J;Fiorina P;Atkinson M;Sayegh MH;Abdi R
通讯作者：
Abdi R
DOI：
10.1111/dme.12850
发表时间：
2015-10
期刊：
Diabetic medicine : a journal of the British Diabetic Association
影响因子：
--
作者：
Kuhtreiber WM;Washer SL;Hsu E;Zhao M;Reinhold P 3rd;Burger D;Zheng H;Faustman DL
通讯作者：
Faustman DL
影响因子：
2.1
作者：
Kim, Nayoun;Cho, Seok-Goo
通讯作者：
Cho, Seok-Goo
影响因子：
5.2
作者：
Abdi, Reza;Moore, Robert;Sakai, Shinobu;Donnelly, Conor B.;Mounayar, Marwan;Sackstein, Robert
通讯作者：
Sackstein, Robert