Department of Clinical Biochemistry, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
Department of Hematology and Cell Therapy, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran; Department of Cell and Molecular Biology, Faculty of Biological Science and Technology, Isfahan University, Isfahan, Iran.
Vitam Horm. 2021;116:235-268. doi: 10.1016/bs.vh.2021.02.006. Epub 2021 Mar 9.
Type 1 diabetes mellitus occurs when beta cell mass is reduced to less than 20% of the normal level due to immune system destruction of beta cell resulting in an inability to secrete enough insulin. The prevalence of diabetes is expanding according to the American Diabetes Association and the World Health Organization (WHO), foretold to exceed 350 million by 2030. The current treatment does not cure many of the serious complications associated with the disease such as neuropathy, nephropathy, dyslipidemia, retinopathy and cardiovascular disease. Whole pancreas or isolated pancreatic islet transplantation as an alternative therapy can prevent or reduce some of the complications of diabetes. However, the shortage of matched organ or islets cells donor and alloimmune responses limit this therapeutic strategy. Recently, several reports have raised extremely promising results to use different sources of stem cells to differentiate insulin-producing cells and focus on the expansion of these alternative sources. Stem cells, due to their potential for multiple differentiation and self-renewal can differentiate into all cell types, including insulin-producing cells (IPCs). Generation of new beta cells can be achieved from various stem cell sources, including embryonic stem cells (ESCs), adult stem cells, such as mesenchymal stem cells (MSCs) and induced pluripotent stem cells (iPSCs). Thus, this chapter discusses on the assistance of cellular reprogramming of various stem cells as candidates for the generation of IPCs using transcription factors/miRNA, cytokines/small molecules and tissue engineering.
1 型糖尿病是由于免疫系统破坏β细胞,导致β细胞数量减少到正常水平的 20%以下,从而无法分泌足够的胰岛素而发生的。根据美国糖尿病协会和世界卫生组织(WHO)的预测,糖尿病的患病率正在扩大,到 2030 年将超过 3.5 亿。目前的治疗方法并不能治愈许多与疾病相关的严重并发症,如神经病变、肾病、血脂异常、视网膜病变和心血管疾病。全胰腺或分离胰岛移植作为替代治疗方法可以预防或减少糖尿病的一些并发症。然而,匹配的器官或胰岛细胞供体的短缺和同种免疫反应限制了这种治疗策略。最近,有几项报告提出了非常有希望的结果,即使用不同来源的干细胞来分化产生胰岛素的细胞,并专注于这些替代来源的扩增。干细胞由于其多向分化和自我更新的潜力,可以分化为所有细胞类型,包括产生胰岛素的细胞(IPCs)。从各种干细胞来源,包括胚胎干细胞(ESCs)、间充质干细胞(MSCs)和诱导多能干细胞(iPSCs),可以产生新的β细胞。因此,本章讨论了使用转录因子/miRNA、细胞因子/小分子和组织工程,对各种干细胞进行细胞重编程,作为生成 IPCs 的候选方法。