Miszta-Lane Helena, Mirbolooki Mohammadreza, James Shapiro A M, Lakey Jonathan R T
Clinical Islet Transplantation Program, Department of Surgery, Faculty of Medicine and Dentistry, University of Alberta, 1074 Dentistry/Pharmacy Centre, Edmonton, Alta., Canada T6G 2N8.
Med Hypotheses. 2006;67(4):909-13. doi: 10.1016/j.mehy.2006.03.036. Epub 2006 Jun 9.
Lifelong immunosuppressive therapy and inadequate sources of transplantable islets have led the islet transplantation benefits to less than 0.5% of type 1 diabetics. Whereas the potential risk of infection by animal endogenous viruses limits the uses of islet xeno-transplantation, deriving islets from stem cells seems to be able to overcome the current problems of islet shortages and immune compatibility. Both embryonic (derived from the inner cell mass of blastocysts) and adult stem cells (derived from adult tissues) have shown controversial results in secreting insulin in vitro and normalizing hyperglycemia in vivo. ESCs research is thought to have much greater developmental potential than adult stem cells; however it is still in the basic research phase. Existing ESC lines are not believed to be identical or ideal for generating islets or beta-cells and additional ESC lines have to be established. Research with ESCs derived from humans is controversial because it requires the destruction of a human embryo and/or therapeutic cloning, which some believe is a slippery slope to reproductive cloning. On the other hand, adult stem cells are already in some degree specialized, recipients may receive their own stem cells. They are flexible but they have shown mixed degree of availability. Adult stem cells are not pluripotent. They may not exist for all organs. They are difficult to purify and they cannot be maintained well outside the body. In order to draw the future avenues in this field, existent discrepancies between the results need to be clarified. In this study, we will review the different aspects and challenges of using embryonic or adult stem cells in clinical islet transplantation for the treatment of type 1 diabetes.
终身免疫抑制治疗以及可移植胰岛来源不足,导致胰岛移植仅使不到0.5%的1型糖尿病患者受益。而动物内源性病毒感染的潜在风险限制了胰岛异种移植的应用,从干细胞中获取胰岛似乎能够克服当前胰岛短缺和免疫相容性方面的问题。胚胎干细胞(源自囊胚的内细胞团)和成体干细胞(源自成体组织)在体外分泌胰岛素及在体内使高血糖正常化方面均呈现出有争议的结果。胚胎干细胞研究被认为比成体干细胞具有更大的发育潜力;然而,它仍处于基础研究阶段。现有的胚胎干细胞系被认为并非完全相同或并非理想的用于生成胰岛或β细胞的细胞系,因此必须建立更多的胚胎干细胞系。对源自人类的胚胎干细胞进行研究存在争议,因为这需要破坏人类胚胎和/或治疗性克隆,一些人认为这是走向生殖克隆的危险斜坡。另一方面,成体干细胞已经在一定程度上实现了特化,受体可能接受自身的干细胞。它们具有灵活性,但可用性程度不一。成体干细胞并非多能性的。并非所有器官都有成体干细胞。它们难以纯化,且在体外难以良好维持。为了明确该领域未来的发展方向,需要澄清现有结果之间的差异。在本研究中,我们将综述在临床胰岛移植中使用胚胎干细胞或成体干细胞治疗1型糖尿病的不同方面及挑战。