Lo Kwee-Seong Integrated Biomedical Sciences Building, Room 609A, School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong, China.
Curr Mol Med. 2013 Jan;13(1):109-25.
Diabetes is characterized by insulin deficiency concomitant with hyperglycemia due to reduced islet cell mass and/or dysfunction. Currently, insulin replacement is the first-line treatment option for patients with type 1 and a severe form of type 2 diabetes. Treatment by insulin injection is generally effective but nonphysiological, and has the potential of producing chronic complications. On the other hand, islet transplantation can maintain normoglycemia without hypoglycemic side effects, potentially freeing diabetic patients of insulin dependence. In practice, islet transplantation remains hindered by the lack of organ donors and transplant rejection concerns. Recent advances in stem cell research and regenerative medicine, however, offer promise for the clinical application of islet cell transplantation. This review article offers a critical appraisal of current molecular induction approaches, such as directed differentiation, microenvironment induction, and genetic modification, which mimic islet cell development by inducing a variety of stem cells; they include embryonic stem cells, induced pluripotent stem cells, and various tissue-derived stem cells to become functional and transplantable insulin-producing islet cells. Despite good progress, several obstacles remain to be overcome before islet transplantation can be translated into a therapy for human patients, including, but are not limited to, immunogenicity and risk of tumorogenesis.
糖尿病的特征是由于胰岛细胞数量减少和/或功能障碍导致胰岛素缺乏伴高血糖。目前，胰岛素替代疗法是 1 型和严重 2 型糖尿病患者的首选治疗方法。胰岛素注射治疗通常有效但非生理性，并有产生慢性并发症的潜在风险。另一方面，胰岛移植可以在不产生低血糖副作用的情况下维持正常血糖水平，有可能使糖尿病患者摆脱对胰岛素的依赖。然而，在实践中，胰岛移植仍然受到器官供体缺乏和移植排斥反应的限制。近年来，干细胞研究和再生医学的进展为胰岛细胞移植的临床应用提供了希望。本文对目前的分子诱导方法进行了批判性评价，如定向分化、微环境诱导和遗传修饰，这些方法通过诱导各种干细胞（包括胚胎干细胞、诱导多能干细胞和各种组织来源的干细胞）成为功能性和可移植的胰岛素产生胰岛细胞，模拟胰岛细胞的发育。尽管取得了良好的进展，但在胰岛移植转化为人类患者的治疗方法之前，仍有几个障碍需要克服，包括免疫原性和肿瘤发生的风险。
