Syngeneically transplanted insulin producing cells differentiated from adipose derived stem cells undergo delayed damage by autoimmune responses in NOD mice.
Syngeneically transplanted insulin producing cells differentiated from adipose derived stem cells undergo delayed damage by autoimmune responses in NOD mice.
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DOI：
10.1038/s41598-022-09838-x
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发表时间：
2022-04-07
影响因子：
4.6
通讯作者：
Shimada M
中科院分区：
文献类型：
--
作者：
Tokuda K;Ikemoto T;Yamashita S;Miyazaki K;Okikawa S;Yamada S;Saito Y;Morine Y;Shimada M
由我们建立的方案产生的胰岛素产生细胞（IPC）已经达到了非临床的“概念验证”阶段。我们的临床应用策略是将IPC自体移植到1型糖尿病（T1DM）患者中。在这种情况下，T1DM的特征性自身免疫是重要的，而不是同种异体排斥。我们的目的是确定这些IPC如何响应T1DM自身免疫。使用我们的方案从非肥胖糖尿病（NOD）小鼠的皮下脂肪组织产生IPC。在糖尿病发作时，将来自NOD小鼠的IPC移植到NOD小鼠的肾包膜下，并表征随后血糖浓度的变化。移植后30天内血糖下降，但在4只受体NOD小鼠中的3只中，40 - 60天后血糖再次升高。在组织样本中，移植后60天的CD4+和CD8 + T细胞的数量显著高于移植后30天。总之，IPC在短期内显着改善小鼠的糖尿病，但在长期内被自身免疫损伤，如局部T细胞积累所证明的。这项研究为T1DM的潜在干细胞疗法提供了新的见解。
Insulin-producing cells (IPCs) generated by our established protocol have reached the non-clinical ‘proof of concept’ stage. Our strategy for their clinical application is the autotransplantation of IPCs into patients with type 1 diabetes mellitus (T1DM). In this context, the autoimmunity that characterized T1DM is important, rather than allorejection. We aimed to determine how these IPCs respond to T1DM autoimmunity. IPCs were generated from the subcutaneous fat tissue of non-obese diabetic (NOD) mice using our protocol. IPCs derived from NOD mice were transplanted under the kidney capsules of NOD mice at the onset of diabetes and the subsequent changes in blood glucose concentration were characterized. Blood glucose decreased within 30 days of transplantation, but increased again after 40–60 days in three of four recipient NOD mice. In tissue samples, the numbers of CD4+ and CD8+ T cells were significantly higher 60 days after transplantation than 30 days after transplantation. In conclusion, IPCs significantly ameliorate the diabetes of mice in the short term, but are damaged by autoimmunity in the longer term, as evidenced by local T cells accumulation. This study provides new insights into potential stem cell therapies for T1DM.
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影响因子：
7.3
作者：
Kroger CJ;Clark M;Ke Q;Tisch RM
通讯作者：
Tisch RM
影响因子：
3.3
作者：
Tokuda K;Ikemoto T;Saito Y;Miyazaki K;Yamashita S;Yamada S;Imura S;Morine Y;Shimada M
通讯作者：
Shimada M
影响因子：
6
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Arzouni, Ahmed A.;Vargas-Seymour, Andreia;Jones, Peter M.
通讯作者：
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影响因子：
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Osum KC;Burrack AL;Martinov T;Sahli NL;Mitchell JS;Tucker CG;Pauken KE;Papas K;Appakalai B;Spanier JA;Fife BT
通讯作者：
Fife BT
影响因子：
7.7
作者：
Hayward, Julie A.;Ellis, Cara E.;Korbutt, Gregory S.
通讯作者：
Korbutt, Gregory S.