Implantable niche with local immunosuppression for islet allotransplantation achieves type 1 diabetes reversal in rats.
Implantable niche with local immunosuppression for islet allotransplantation achieves type 1 diabetes reversal in rats.
复制标题
具有局部免疫抑制的植入式生态裂市场，用于同种异体移植的胰岛，可实现大鼠的1型糖尿病逆转。
DOI：
10.1038/s41467-022-35629-z
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发表时间：
2022-12-26
影响因子：
16.6
通讯作者：
Grattoni, Alessandro
中科院分区：
文献类型：
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作者：
Paez-Mayorga, Jesus;Campa-Carranza, Jocelyn Nikita;Capuani, Simone;Hernandez, Nathanael;Liu, Hsuan-Chen;Chua, Corrine Ying Xuan;Pons-Faudoa, Fernanda Paola;Malgir, Gulsah;Alvarez, Bella;Niles, Jean A.;Argueta, Lissenya B.;Shelton, Kathryn A.;Kezar, Sarah;Nehete, Pramod N.;Berman, Dora M.;Willman, Melissa A.;Li, Xian C.;Ricordi, Camillo;Nichols, Joan E.;Gaber, A. Osama;Kenyon, Norma S.;Grattoni, Alessandro
胰岛移植治疗1型糖尿病（T1D）的疗效受到缺氧相关移植物磨损和需要全身免疫抑制的限制。为了克服这些挑战，我们开发了新血管化可植入细胞归巢和封装（NICHE）装置，该装置集成了直接血管化以便于质量转移和局部免疫抑制剂递送以预防胰岛排斥。在此，我们研究了免疫活性雄性大鼠模型中NICHE对同种异体胰岛移植和长期糖尿病逆转的疗效。我们证明了移植在预血管化的NICHE内的同种异体胰岛在大鼠中被移植、再血管化和功能性逆转糖尿病超过150天。值得注意的是，我们证实了局部免疫抑制可以防止胰岛排斥反应，而不会引起毒性或全身免疫抑制。此外，对于可翻译性的努力，我们显示了NICHE的生物相容性和部署的可行性，以及在MHC不匹配的非人灵长类动物模型中的短期同种异体胰岛移植。总之，NICHE有望成为安全有效的胰岛移植和长期T1D管理的可行方法。胰岛移植治疗1型糖尿病受到终身免疫抑制药物需求的阻碍。在这里，作者报告了一种具有局部抗排斥药物释放的胰岛封装装置，该装置可实现雄性大鼠的长期糖尿病逆转并降低药物相关毒性。
Pancreatic islet transplantation efficacy for type 1 diabetes (T1D) management is limited by hypoxia-related graft attrition and need for systemic immunosuppression. To overcome these challenges, we developed the Neovascularized Implantable Cell Homing and Encapsulation (NICHE) device, which integrates direct vascularization for facile mass transfer and localized immunosuppressant delivery for islet rejection prophylaxis. Here, we investigated NICHE efficacy for allogeneic islet transplantation and long-term diabetes reversal in an immunocompetent, male rat model. We demonstrated that allogeneic islets transplanted within pre-vascularized NICHE were engrafted, revascularized, and functional, reverting diabetes in rats for over 150 days. Notably, we confirmed that localized immunosuppression prevented islet rejection without inducing toxicity or systemic immunosuppression. Moreover, for translatability efforts, we showed NICHE biocompatibility and feasibility of deployment as well as short-term allogeneic islet engraftment in an MHC-mismatched nonhuman primate model. In sum, the NICHE holds promise as a viable approach for safe and effective islet transplantation and long-term T1D management. Islet transplantation for type 1 diabetes management is hindered by the life-long need for immunosuppressive medications. Here, the authors report an islet encapsulation device with local anti-rejection drug release that achieves long-term diabetes reversal in male rats and reduces drug-related toxicity.
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DOI：
10.1136/jnnp-2021-327480
发表时间：
2022-03
期刊：
Journal of neurology, neurosurgery, and psychiatry
影响因子：
--
作者：
Ferrari MD;Reuter U;Goadsby PJ;Paiva da Silva Lima G;Mondal S;Wen S;Tenenbaum N;Pandhi S;Lanteri-Minet M;Stites T
通讯作者：
Stites T
影响因子：
3.9
作者：
Bottino, Rita;Knoll, Michael F.;Cooper, David K. C.
通讯作者：
Cooper, David K. C.
影响因子：
38.3
作者：
Burke JA;Zhang X;Bobbala S;Frey MA;Bohorquez Fuentes C;Freire Haddad H;Allen SD;Richardson RAK;Ameer GA;Scott EA
通讯作者：
Scott EA
影响因子：
28.1
作者：
Doloff, Joshua C.;Veiseh, Omid;Langer, Robert
通讯作者：
Langer, Robert
DOI：
10.1007/978-3-319-39824-2_5
发表时间：
2016-01-01
期刊：
PANCREATIC ISLET ISOLATION: FROM THE MOUSE TO THE CLINIC
影响因子：
--
作者：
Berman, Dora M.
通讯作者：
Berman, Dora M.