Benthuysen Jacqueline R, Carrano Andrea C, Sander Maike
J Clin Invest. 2016 Oct 3;126(10):3651-3660. doi: 10.1172/JCI87439.
In the past decade, new approaches have been explored that are aimed at restoring functional β cell mass as a treatment strategy for diabetes. The two most intensely pursued strategies are β cell replacement through conversion of other cell types and β cell regeneration by enhancement of β cell replication. The approach closest to clinical implementation is the replacement of β cells with human pluripotent stem cell-derived (hPSC-derived) cells, which are currently under investigation in a clinical trial to assess their safety in humans. In addition, there has been success in reprogramming developmentally related cell types into β cells. Reprogramming approaches could find therapeutic applications by inducing β cell conversion in vivo or by reprogramming cells ex vivo followed by implantation. Finally, recent studies have revealed novel pharmacologic targets for stimulating β cell replication. Manipulating these targets or the pathways they regulate could be a strategy for promoting the expansion of residual β cells in diabetic patients. Here, we provide an overview of progress made toward β cell replacement and regeneration and discuss promises and challenges for clinical implementation of these strategies.
在过去十年中，人们探索了一些新方法，旨在恢复功能性β细胞群，作为糖尿病的一种治疗策略。目前最受关注的两种策略是通过其他细胞类型的转化进行β细胞替代，以及通过增强β细胞复制实现β细胞再生。最接近临床应用的方法是用人多能干细胞衍生（hPSC衍生）的细胞替代β细胞，目前正在进行一项临床试验，以评估其在人体中的安全性。此外，已成功地将发育相关的细胞类型重编程为β细胞。重编程方法可通过在体内诱导β细胞转化或在体外重编程细胞后进行植入来找到治疗应用。最后，最近的研究揭示了刺激β细胞复制的新的药理学靶点。操纵这些靶点或它们所调节的途径可能是促进糖尿病患者残余β细胞扩增的一种策略。在此，我们概述了在β细胞替代和再生方面取得的进展，并讨论了这些策略临床应用的前景和挑战。
