Human mesenchymal stem cells protect human islets from pro-inflammatory cytokines.
Human mesenchymal stem cells protect human islets from pro-inflammatory cytokines.
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DOI：
10.1371/journal.pone.0038189
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Korbutt GS
中科院分区：
文献类型：
--
作者：
Yeung TY;Seeberger KL;Kin T;Adesida A;Jomha N;Shapiro AM;Korbutt GS
对于 1 型糖尿病患者来说，人胰岛移植是每日注射胰岛素的一种有吸引力的替代方案。然而，大多数胰岛受体在五年内失去移植功能。炎症是移植物损失的主要原因，抑制促炎细胞因子活性可以逆转炎症介导的胰岛移植物功能障碍。由于间充质干细胞 (MSC) 具有多种免疫调节特性，我们假设 MSC 可以保护人类胰岛免受促炎细胞因子的影响。将 500 个人类胰岛与来自骨髓或胰腺的 0.5 或 1.0×106 个人类 MSC 共培养 24 小时，然后暴露于干扰素-γ、肿瘤坏死因子-α 和白细胞介素 1β 48 小时。对照包括单独培养的胰岛（±细胞因子）和与人真皮成纤维细胞（±细胞因子）一起培养的胰岛。在所有条件下，测定了葡萄糖刺激的胰岛素分泌（GSIS）、总胰岛细胞胰岛素含量、胰岛β细胞凋亡以及培养基中分泌的潜在细胞保护因子。根据刺激指数和胰岛素分泌百分比，细胞因子暴露破坏了人胰岛 GSIS。相反，用 1.0×106 bMSC 培养保留了来自细胞因子处理的胰岛的 GSIS。未观察到成纤维细胞的保护作用，表明暴露于促炎细胞因子后人胰岛 GSIS 的保存是 MSC 依赖性的。在细胞因子存在下观察到胰岛β细胞凋亡；然而，bMSCs 与胰岛的培养可防止细胞因子处理后的 β 细胞凋亡。肝细胞生长因子 (HGF) 以及基质金属蛋白酶 2 和 9 也被鉴定为推定的分泌性细胞保护因子；然而，其他分泌因子可能发挥保护作用。因此，这项研究表明间充质干细胞可能通过促进细胞存活和减少炎症而有益于胰岛移植。
Transplantation of human islets is an attractive alternative to daily insulin injections for patients with type 1 diabetes. However, the majority of islet recipients lose graft function within five years. Inflammation is a primary contributor to graft loss, and inhibiting pro-inflammatory cytokine activity can reverse inflammation mediated dysfunction of islet grafts. As mesenchymal stem cells (MSCs) possess numerous immunoregulatory properties, we hypothesized that MSCs could protect human islets from pro-inflammatory cytokines. Five hundred human islets were co-cultured with 0.5 or 1.0×106 human MSCs derived from bone marrow or pancreas for 24 hours followed by 48 hour exposure to interferon-γ, tumor necrosis factor-α and interleukin 1β. Controls include islets cultured alone (± cytokines) and with human dermal fibroblasts (± cytokines). For all conditions, glucose stimulated insulin secretion (GSIS), total islet cellular insulin content, islet β cell apoptosis, and potential cytoprotective factors secreted in the culture media were determined. Cytokine exposure disrupted human islet GSIS based on stimulation index and percentage insulin secretion. Conversely, culture with 1.0×106 bMSCs preserved GSIS from cytokine treated islets. Protective effects were not observed with fibroblasts, indicating that preservation of human islet GSIS after exposure to pro-inflammatory cytokines is MSC dependent. Islet β cell apoptosis was observed in the presence of cytokines; however, culture of bMSCs with islets prevented β cell apoptosis after cytokine treatment. Hepatocyte growth factor (HGF) as well as matrix metalloproteinases 2 and 9 were also identified as putative secreted cytoprotective factors; however, other secreted factors likely play a role in protection. This study, therefore, demonstrates that MSCs may be beneficial for islet engraftment by promoting cell survival and reduced inflammation.
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影响因子：
0.9
作者：
Park, K. S.;Kim, Y. S.;Kim, S. J.
通讯作者：
Kim, S. J.
影响因子：
8.2
作者：
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Mathieu, C
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1.5
作者：
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Park, CG
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7.7
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Abdi R;Fiorina P;Adra CN;Atkinson M;Sayegh MH
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3.4
作者：
Duprez IR;Johansson U;Nilsson B;Korsgren O;Magnusson PU
通讯作者：
Magnusson PU