Department of Theriogenology and Biotechnology, College of Veterinary Medicine and Research Institute of Life Science, Gyeongsang National University, Jinju 52828, Korea.
Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN 55905, USA.
Int J Mol Sci. 2020 Mar 30;21(7):2388. doi: 10.3390/ijms21072388.
Diabetes is a metabolic disease which affects not only glucose metabolism but also lipid and protein metabolism. It encompasses two major types: type 1 and 2 diabetes. Despite the different etiologies of type 1 and 2 diabetes mellitus (T1DM and T2DM, respectively), the defining features of the two forms are insulin deficiency and resistance, respectively. Stem cell therapy is an efficient method for the treatment of diabetes, which can be achieved by differentiating pancreatic β-like cells. The consistent generation of glucose-responsive insulin releasing cells remains challenging. In this review article, we present basic concepts of pancreatic organogenesis, which intermittently provides a basis for engineering differentiation procedures, mainly based on the use of small molecules. Small molecules are more auspicious than any other growth factors, as they have unique, valuable properties like cell-permeability, as well as a nonimmunogenic nature; furthermore, they offer immense benefits in terms of generating efficient functional beta-like cells. We also summarize advances in the generation of stem cell-derived pancreatic cell lineages, especially endocrine β-like cells or islet organoids. The successful induction of stem cells depends on the quantity and quality of available stem cells and the efficient use of small molecules.
糖尿病是一种代谢性疾病,不仅影响葡萄糖代谢,还影响脂质和蛋白质代谢。它包括两种主要类型:1 型和 2 型糖尿病。尽管 1 型和 2 型糖尿病(T1DM 和 T2DM)的病因不同,但这两种形式的特征分别是胰岛素缺乏和抵抗。干细胞疗法是治疗糖尿病的一种有效方法,可以通过分化胰岛β样细胞来实现。持续生成葡萄糖反应性胰岛素释放细胞仍然具有挑战性。在这篇综述文章中,我们介绍了胰腺发生的基本概念,这些概念为工程分化程序提供了间歇性的基础,主要基于小分子的使用。小分子比任何其他生长因子都更有前途,因为它们具有独特的、有价值的特性,如细胞通透性和非免疫原性;此外,它们在生成高效功能性β样细胞方面具有巨大的优势。我们还总结了干细胞衍生的胰腺细胞谱系,特别是内分泌β样细胞或胰岛类器官的生成方面的进展。干细胞的成功诱导取决于可用干细胞的数量和质量,以及小分子的有效利用。