Successful modulation of type 2 diabetes in db/db mice with intra-bone marrow--bone marrow transplantation plus concurrent thymic transplantation.
Successful modulation of type 2 diabetes in db/db mice with intra-bone marrow--bone marrow transplantation plus concurrent thymic transplantation.
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DOI：
10.1016/j.jaut.2010.09.001
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发表时间：
2010-12
影响因子：
12.8
通讯作者：
Ikehara S
中科院分区：
文献类型：
--
作者：
Li M;Abraham NG;Vanella L;Zhang Y;Inaba M;Hosaka N;Hoshino S;Shi M;Ambrosini YM;Gershwin ME;Ikehara S
越来越多的证据表明，自身免疫和自身炎症机制不仅与 1 型糖尿病 (T1 DM) 的发生有关，而且还与 2 型糖尿病 (T2 DM) 的发生有关。我们实验室一直致力于这一概念，并在早期的工作中通过 IBM-BMT 将瘦素受体缺陷 (db/db) 小鼠（一种 T2DM 动物模型）的骨髓细胞 (BMC) 替换为正常 C57BL/6 (B6) 小鼠的骨髓细胞 (BMC)。然而，由于T细胞功能恢复不完全，结果不佳。因此，我们假设骨髓内-骨髓移植加胸腺移植（IBM-BMT + TT）可通过使 T 细胞失衡正常化来治疗 T2 DM。因此，我们通过使用这种双重移植解决了这个问题，并在此证明七周后，受体db/db小鼠表现出体重改善、血糖水平降低以及血浆IL-6和IL-1β减少。更重要的是，这种治疗方案显示出正常的 CD4/CD8 比率，并增加了血浆脂联素水平、胰岛素敏感性和胰岛素产生细胞的数量。此外，在接受 IBM-BMT + TT 治疗的小鼠中，胰腺 pAKT、pLKB1、pAMPK 和 HO-1 的表达增加。我们的数据显示，IBM–BMT + TT 治疗使 db/db 小鼠的 T 细胞亚群、细胞因子失衡和胰岛素敏感性正常化，表明 IBM–BMT + TT 是治疗 T2 DM 的可行治疗选择。
There is increasing evidence that both autoimmune and autoinflammatory mechanisms are involved in the development of not only type 1 diabetes mellitus (T1 DM), but also type 2 diabetes mellitus (T2 DM). Our laboratory has focused on this concept, and in earlier efforts replaced the bone marrow cells (BMCs) of leptin receptor-deficient (db/db) mice, an animal model of T2DM, with those of normal C57BL/6 (B6) mice by IBM–BMT. However, the outcome was poor due to incomplete recovery of T cell function. Therefore, we hypothesized that intra-bone marrow–bone marrow transplantation plus thymus transplantation (IBM–BMT + TT) could be used to treat T2 DM by normalizing the T cell imbalance. Hence we addressed this issue by using such dual transplantation and demonstrate herein that seven weeks later, recipient db/db mice manifested improved body weight, reduced levels of blood glucose, and a reduction of plasma IL-6 and IL-1 β. More importantly, this treatment regimen showed normal CD4/CD8 ratios, and increased plasma adiponectin levels, insulin sensitivity, and the number of insulin-producing cells. Furthermore, the expression of pancreatic pAKT, pLKB1, pAMPK and HO-1 was increased in the mice treated with IBM–BMT + TT. Our data show that IBM–BMT + TT treatment normalizes T cell subsets, cytokine imbalance and insulin sensitivity in the db/db mouse, suggesting that IBM–BMT + TT is a viable therapeutic option in the treatment of T2 DM.
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DOI：
10.1073/pnas.93.16.8558
发表时间：
1996-08-06
影响因子：
11.1
作者：
Hosaka, N;Nose, M;Ikehara, S
通讯作者：
Ikehara, S
影响因子：
12.8
作者：
Hara, Mayumi;Murakami, Takashi;Kobayashi, Eiji
通讯作者：
Kobayashi, Eiji
影响因子：
6.1
作者：
Kimura, M;Tanaka, S;Sekihari, H
通讯作者：
Sekihari, H
影响因子：
19.6
作者：
Chow, F;Ozols, E;Tesch, GH
通讯作者：
Tesch, GH
影响因子：
12.8
作者：
Deane, Sean;Meyers, Frederick J.;Gershwin, M. Eric
通讯作者：
Gershwin, M. Eric