Diabetes affects almost half a billion people, and all individuals with type 1 diabetes (T1D) and a large portion of individuals with type 2 diabetes rely on self-administration of the peptide hormone insulin to achieve glucose control. However, this treatment modality has cumbersome storage and equipment requirements and is susceptible to fatal user error. Here, reasoning that a cell-based therapy could be coupled to an external induction circuit for blood glucose control, as a proof of concept we developed far-red light (FRL)-activated human islet-like designer (FAID) cells and demonstrated how FAID cell implants achieved safe and sustained glucose control in diabetic model mice. Specifically, by introducing a FRL-triggered optogenetic device into human mesenchymal stem cells (hMSCs), which we encapsulated in poly-(l-lysine)-alginate and implanted subcutaneously under the dorsum of T1D model mice, we achieved FRL illumination-inducible secretion of insulin that yielded improvements in glucose tolerance and sustained blood glucose control over traditional insulin glargine treatment. Moreover, the FAID cell implants attenuated both oxidative stress and development of multiple diabetes-related complications in kidneys. This optogenetics-controlled “living cell factory” platform could be harnessed to develop multiple synthetic designer therapeutic cells to achieve long-term yet precisely controllable drug delivery.

糖尿病影响了近 50 亿人，所有 1 型糖尿病 (T1D) 患者和大部分 2 型糖尿病患者都依赖肽激素胰岛素的自我给药来实现血糖控制。然而，这种治疗方式具有繁琐的存储和设备要求，并且容易出现致命的用户错误。在这里，推理基于细胞的疗法可以耦合到用于血糖控制的外部感应电路，作为概念证明，我们开发了远红光 (FRL) 激活的人类胰岛样设计 (FAID) 细胞并演示了如何FAID 细胞植入物在糖尿病模型小鼠中实现了安全和持续的血糖控制。具体来说，通过将 FRL 触发的光遗传学装置引入人间充质干细胞 (hMSC)，我们将其封装在聚 ( l-赖氨酸)-藻酸盐并皮下植入 T1D 模型小鼠的背部，我们实现了 FRL 光照诱导的胰岛素分泌，与传统的甘精胰岛素治疗相比，它改善了葡萄糖耐量和持续的血糖控制。此外，FAID 细胞植入物减轻了氧化应激和肾脏中多种糖尿病相关并发症的发展。这种光遗传学控制的“活细胞工厂”平台可用于开发多种合成设计治疗细胞，以实现长期但精确可控的药物输送。