Center of Biomedical Investigation (CIBUS), Universidad de La Sabana, Chia 250008, Colombia.
Doctoral Program in Biociencias, Universidad de La Sabana, Chia 250008, Colombia.
Int J Mol Sci. 2024 Sep 6;25(17):9654. doi: 10.3390/ijms25179654.
Diabetes mellitus, a chronic and non-transmissible disease, triggers a wide range of micro- and macrovascular complications. The differentiation of pancreatic β-like cells (PβLCs) from induced pluripotent stem cells (iPSCs) offers a promising avenue for regenerative medicine aimed at treating diabetes. Current differentiation protocols strive to emulate pancreatic embryonic development by utilizing cytokines and small molecules at specific doses to activate and inhibit distinct molecular signaling pathways, directing the differentiation of iPSCs into pancreatic β cells. Despite significant progress and improved protocols, the full spectrum of molecular signaling pathways governing pancreatic development and the physiological characteristics of the differentiated cells are not yet fully understood. Here, we report a specific combination of cofactors and small molecules that successfully differentiate iPSCs into PβLCs. Our protocol has shown to be effective, with the resulting cells exhibiting key functional properties of pancreatic β cells, including the expression of crucial molecular markers (pdx1, nkx6.1, ngn3) and the capability to secrete insulin in response to glucose. Furthermore, the addition of vitamin C and retinoic acid in the final stages of differentiation led to the overexpression of specific β cell genes.
糖尿病是一种慢性且非传染性疾病，会引发多种微血管和大血管并发症。诱导多能干细胞（iPSC）分化为胰岛β样细胞（PβLC）为治疗糖尿病的再生医学提供了有前途的途径。目前的分化方案通过使用特定剂量的细胞因子和小分子来模拟胰腺胚胎发育，激活和抑制不同的分子信号通路，指导 iPSC 分化为胰腺β细胞。尽管取得了重大进展和改进的方案，但调控胰腺发育和分化细胞的生理特征的分子信号通路的全貌尚未完全了解。在这里，我们报告了一种特定的共因子和小分子组合，可成功地将 iPSC 分化为 PβLC。我们的方案已被证明是有效的，所得到的细胞表现出胰腺β细胞的关键功能特性，包括表达关键的分子标记物（pdx1、nkx6.1、ngn3）以及能够响应葡萄糖分泌胰岛素。此外，在分化的最后阶段添加维生素 C 和视黄酸导致特定β细胞基因的过表达。
