Hypoimmune islets achieve insulin independence after allogeneic transplantation in a fully immunocompetent non-human primate.

Cell stem cell Pub Date : 2024-03-07 Epub Date: 2024-02-08 DOI:10.1016/j.stem.2024.02.001
Xiaomeng Hu, Kathy White, Chi Young, Ari G Olroyd, Paul Kievit, Andrew J Connolly, Tobias Deuse, Sonja Schrepfer
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Abstract

Allogeneic transplantation of pancreatic islets for patients with difficult-to-control diabetes mellitus is severely hampered by the requirement for continuous immunosuppression and its associated morbidity. We report that allogeneic transplantation of genetically engineered (B2M-/-, CIITA-/-, CD47+), primary, hypoimmune, pseudo-islets (p-islets) results in their engraftment into a fully immunocompetent, diabetic non-human primate wherein they provide stable endocrine function and enable insulin independence without inducing any detectable immune response in the absence of immunosuppression. Hypoimmune primary p-islets may provide a curative cell therapy for type 1 diabetes mellitus.

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免疫力低下的胰岛在完全免疫功能健全的非人灵长类动物体内进行异体移植后实现了胰岛素独立性。
为难以控制的糖尿病患者进行异体胰岛移植,由于需要持续的免疫抑制及其相关的发病率而受到严重阻碍。我们报告说,异体移植基因工程(B2M-/-、CIITA-/-、CD47+)、原发性、低免疫性、假性胰岛(p-islets)可将其移植到完全免疫功能健全的非人类糖尿病灵长类动物体内,在没有免疫抑制的情况下,这些胰岛可提供稳定的内分泌功能并实现胰岛素独立,而不会诱发任何可检测到的免疫反应。免疫力低下的原发性 p-islets 可为 1 型糖尿病提供一种治疗性细胞疗法。
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