Abstract：
The loss or dysfunction of pancreatic β-cells, which are responsible for insulin secretion, constitutes the foundation of all forms of diabetes, a widely prevalent disease worldwide. The replacement of damaged β-cells with regenerated or transplanted cells derived from stem cells is a promising therapeutic strategy. However, inducing the differentiation of stem cells into fully functional glucose-responsive β-cells in vitro has proven to be challenging. Noncoding RNAs (ncRNAs) have emerged as critical regulatory factors governing the differentiation, identity, and function of β-cells. Furthermore, engineered hydrogel systems, biomaterials, and organ-like structures possess engineering characteristics that can provide a three-dimensional (3D) microenvironment that supports stem cell differentiation. This review summarizes the roles and contributions of ncRNAs in maintaining the differentiation, identity, and function of β-cells. And it focuses on regulating the levels of ncRNAs in stem cells to activate β-cell genetic programs for generating alternative β-cells and discusses how to manipulate ncRNA expression by combining hydrogel systems and other tissue engineering materials. Elucidating the patterns of ncRNA-mediated regulation in β-cell biology and utilizing this knowledge to control stem cell differentiation may offer promising therapeutic strategies for generating functional insulin-producing cells in diabetes cell replacement therapy and tissue engineering.
摘要：
胰腺β细胞的丢失或功能障碍，负责胰岛素分泌，构成了所有形式的糖尿病的基础，全世界广泛流行的疾病。用源自干细胞的再生或移植细胞替代受损的β细胞是一种有前途的治疗策略。然而,在体外诱导干细胞分化为功能齐全的葡萄糖反应β细胞已被证明是具有挑战性的。非编码RNA（ncRNAs）已经成为控制分化的关键调节因子，身份，和β细胞的功能。此外，工程水凝胶系统，生物材料,和器官样结构具有可提供支持干细胞分化的三维(3D)微环境的工程特性。这篇综述总结了ncRNAs在维持分化中的作用和贡献，身份，和β细胞的功能。它专注于调节干细胞中ncRNAs的水平，以激活β细胞遗传程序来产生替代β细胞，并讨论如何通过结合水凝胶系统和其他组织工程材料来操纵ncRNA表达。阐明β细胞生物学中ncRNA介导的调节模式并利用这些知识控制干细胞分化可能为糖尿病细胞替代疗法和组织工程中产生功能性胰岛素产生细胞提供有希望的治疗策略。
