Johannesson Bjarki, Sui Lina, Freytes Donald O, Creusot Remi J, Egli Dieter
The New York Stem Cell Foundation Research Institute, New York, NY, USA.
Naomi Berrie Diabetes Center & Department of Pediatrics, College of Physicians and Surgeons, Columbia University, New York, NY, USA.
EMBO J. 2015 Apr 1;34(7):841-55. doi: 10.15252/embj.201490685. Epub 2015 Mar 1.
The discovery of insulin more than 90 years ago introduced a life-saving treatment for patients with type 1 diabetes, and since then, significant progress has been made in clinical care for all forms of diabetes. However, no method of insulin delivery matches the ability of the human pancreas to reliably and automatically maintain glucose levels within a tight range. Transplantation of human islets or of an intact pancreas can in principle cure diabetes, but this approach is generally reserved for cases with simultaneous transplantation of a kidney, where immunosuppression is already a requirement. Recent advances in cell reprogramming and beta cell differentiation now allow the generation of personalized stem cells, providing an unlimited source of beta cells for research and for developing autologous cell therapies. In this review, we will discuss the utility of stem cell-derived beta cells to investigate the mechanisms of beta cell failure in diabetes, and the challenges to develop beta cell replacement therapies. These challenges include appropriate quality controls of the cells being used, the ability to generate beta cell grafts of stable cellular composition, and in the case of type 1 diabetes, protecting implanted cells from autoimmune destruction without compromising other aspects of the immune system or the functionality of the graft. Such novel treatments will need to match or exceed the relative safety and efficacy of available care for diabetes.
90多年前胰岛素的发现为1型糖尿病患者带来了一种挽救生命的治疗方法，从那时起，各种形式糖尿病的临床护理都取得了重大进展。然而，没有一种胰岛素给药方法能与人类胰腺在狭窄范围内可靠且自动维持血糖水平的能力相匹配。移植人类胰岛或完整的胰腺原则上可以治愈糖尿病，但这种方法通常只用于同时进行肾脏移植的病例，因为在这种情况下免疫抑制是必需的。细胞重编程和β细胞分化方面的最新进展现在使得个性化干细胞的产生成为可能，为研究和开发自体细胞疗法提供了无限的β细胞来源。在这篇综述中，我们将讨论干细胞衍生的β细胞在研究糖尿病中β细胞功能衰竭机制方面的效用，以及开发β细胞替代疗法所面临的挑战。这些挑战包括对所用细胞进行适当的质量控制、生成具有稳定细胞组成的β细胞移植物的能力，以及在1型糖尿病的情况下，在不损害免疫系统其他方面或移植物功能的前提下，保护植入细胞免受自身免疫破坏。这种新型治疗方法需要达到或超过现有糖尿病护理的相对安全性和有效性。
