Engineered immunomodulatory accessory cells improve experimental allogeneic islet transplantation without immunosuppression.
Engineered immunomodulatory accessory cells improve experimental allogeneic islet transplantation without immunosuppression.
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DOI：
10.1126/sciadv.abn0071
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发表时间：
2022-07-22
期刊：
影响因子：
13.6
通讯作者：
中科院分区：
文献类型：
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胰岛移植已被确立为1型糖尿病的可行治疗方式。然而，患者所需的全身免疫抑制的副作用往往超过其益处。在这里，我们工程师程序性死亡配体-1和细胞毒性T淋巴细胞抗原4免疫球蛋白融合蛋白修饰的间充质基质细胞（MSC）作为胰岛共移植的辅助细胞。工程化的MSC（eMSC）改善了糖尿病小鼠中同基因和异基因胰岛移植的结果，并导致同种异体移植物存活长达100天，而没有任何全身性免疫抑制。免疫表型分析显示，与对照组相比，与eMSCs共移植的同种异体移植物中CD 4+或CD 8 + T效应细胞浸润减少，T调节细胞浸润增加。结果表明，eMSCs可以诱导局部免疫调节，并可能适用于临床胰岛移植，以减少或最大限度地减少全身免疫抑制的需要，并改善其负面影响。PD-L1/CTLA 4-Ig过表达间充质基质细胞与胰岛移植延长胰岛存活而无免疫抑制。
Islet transplantation has been established as a viable treatment modality for type 1 diabetes. However, the side effects of the systemic immunosuppression required for patients often outweigh its benefits. Here, we engineer programmed death ligand-1 and cytotoxic T lymphocyte antigen 4 immunoglobulin fusion protein–modified mesenchymal stromal cells (MSCs) as accessory cells for islet cotransplantation. The engineered MSCs (eMSCs) improved the outcome of both syngeneic and allogeneic islet transplantation in diabetic mice and resulted in allograft survival for up to 100 days without any systemic immunosuppression. Immunophenotyping revealed reduced infiltration of CD4+ or CD8+ T effector cells and increased infiltration of T regulatory cells within the allografts cotransplanted with eMSCs compared to controls. The results suggest that the eMSCs can induce local immunomodulation and may be applicable in clinical islet transplantation to reduce or minimize the need of systemic immunosuppression and ameliorate its negative impact. PD-L1/CTLA4-Ig–overexpressing mesenchymal stromal cells transplanted with islets prolong islet survival without immunosuppression.
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影响因子：
8.8
作者：
Hernandez-Fisac, I.;Pizarro-Delgado, J.;Tamarit-Rodriguez, J.
通讯作者：
Tamarit-Rodriguez, J.
影响因子：
30.5
作者：
Grohmann, U;Orabona, C;Puccetti, P
通讯作者：
Puccetti, P
DOI：
10.1038/s41573-019-0041-4
发表时间：
2019-10
期刊：
Nature reviews. Drug discovery
影响因子：
--
作者：
Ferreira LMR;Muller YD;Bluestone JA;Tang Q
通讯作者：
Tang Q
影响因子：
4.1
作者：
Graham, John G.;Zhang, Xiaomin;Shea, Lonnie D.
通讯作者：
Shea, Lonnie D.
影响因子：
8.8
作者：
Arnold, R.;Pussell, B. A.;Krishnan, A. V.
通讯作者：
Krishnan, A. V.