Cunha Joao P M C M, Gysemans Conny, Gillard Pieter, Mathieu Chantal
KULEUVEN - Clinical and Experimental Endocrinology, Leuven. Belgium.
Curr Diabetes Rev. 2018;14(1):3-13. doi: 10.2174/1573399812666160629094031.
Beta-cell replacement by human islets or whole pancreas offers a life-saving therapeutic remedy for patients suffering from type 1 diabetes, providing considerable advantages with respect to diminishing total daily insulin dose and lowering frequencies of debilitating hypoglycemic reactions as well as preventing chronic micro- and macrovascular complications. Although remarkable progress has been made in this area, several hurdles remain, hampering its wide-spread applicability. Such hurdles include a limiting supply of islets, the necessity of several donors to achieve enough islet mass for insulin independence, and graft failure because of metabolic pressure, continued autoimmunity, alloimmunity, high concentrations of immunosuppressive drugs as well as oxidative stress caused by hypoxia or inflammation. On the other hand, the islet transplant procedure provides the possibility to undertake multiple practical and beneficial manipulations of the beta cells before engraftment with the intention to reach improved graft survival results.
We have focused on the current status of various obstacles in islet transplantation and on the potential of (stem)cell-based treatments able to stimulate islet graft outcome in pre-clinical and clinical transplantation settings in which specific attention is given to the engraftment-enhancing and immunomodulatory potential of various types of stem cells..
用人胰岛或全胰腺进行β细胞替代为1型糖尿病患者提供了一种挽救生命的治疗方法,在减少每日胰岛素总剂量、降低衰弱性低血糖反应频率以及预防慢性微血管和大血管并发症方面具有显著优势。尽管该领域已取得显著进展,但仍存在一些障碍,阻碍了其广泛应用。这些障碍包括胰岛供应有限、需要多个供体以获得足够的胰岛质量来实现胰岛素自主分泌,以及由于代谢压力、持续的自身免疫、同种免疫、高浓度免疫抑制药物以及缺氧或炎症引起的氧化应激导致的移植失败。另一方面,胰岛移植程序提供了在植入前对β细胞进行多种实际且有益操作的可能性,以期提高移植存活结果。
我们关注了胰岛移植中各种障碍的现状以及基于(干)细胞的治疗方法在临床前和临床移植环境中刺激胰岛移植结果的潜力,其中特别关注了各种类型干细胞的植入增强和免疫调节潜力。