Shaanxi Branch of National Stem Cell Engineering and Technology Centre, College of Veterinary Medicine, Northwest A&F University, Yangling, 712100, Shaanxi, China.
Baiopai (Tianjin) Biotechnology Co., LTD, Jinnan District, Tianjin, 300350, China.
Stem Cell Res Ther. 2022 Jul 28;13(1):370. doi: 10.1186/s13287-022-03020-w.
Islet transplantation is an excellent method for the treatment of type I diabetes mellitus. However, due to the limited number of donors, cumbersome isolation and purification procedures, and immune rejection, the clinical application is greatly limited. The development of a simple and efficient new method to obtain islet β-cells is a key problem that urgently requires a solution for the treatment of type I diabetes mellitus.
In this study, Pbx1, Rfx3, Pdx1, Ngn3, Pax4 and MafA were used to form a six-gene combination to efficiently reprogram aMSCs (adipose mesenchymal stem cells) into ra-βCs (reprogrammed aMSCs-derived islet β-cells), and the characteristics and immunogenicity of ra-βCs were detected. Feasibility of ra-βCs transplantation for the treatment of diabetes mellitus in model dogs and clinical dogs was detected.
In this study, aMSCs were efficiently reprogrammed into ra-βCs using a six-gene combination. The ra-βCs showed islet β-cell characteristics. The immunogenicity of ra-βCs was detected and remained low in vitro and increased after transplantation. The cotransplantation of ra-βCs and aMSCs in the treatment of a model and clinical cases of canine diabetes mellitus achieved ideal therapeutic effects.
The aMSCs were efficiently reprogrammed into ra-βCs using a six-gene combination. The cotransplantation of ra-βCs and aMSCs as a treatment for canine diabetes is feasible, which provides a theoretical basis and therapeutic method for the treatment of canine diabetes.
胰岛移植是治疗 1 型糖尿病的一种极好方法。然而，由于供体数量有限、分离和纯化过程繁琐以及免疫排斥等问题，其临床应用受到了极大限制。开发一种简单高效的新方法来获得胰岛β细胞是解决 1 型糖尿病治疗的关键问题。
本研究采用 Pbx1、Rfx3、Pdx1、Ngn3、Pax4 和 MafA 组成的六基因组合，高效重编程 aMSCs（脂肪间充质干细胞）为 ra-βCs（重编程 aMSCs 衍生的胰岛 β 细胞），并检测 ra-βCs 的特性和免疫原性。检测 ra-βCs 移植治疗模型犬和临床犬糖尿病的可行性。
本研究采用六基因组合高效重编程 aMSCs 为 ra-βCs。ra-βCs 表现出胰岛 β 细胞特征。检测了 ra-βCs 的免疫原性，结果表明其在体外保持低水平，移植后升高。ra-βCs 和 aMSCs 的共移植治疗犬糖尿病模型和临床病例取得了理想的治疗效果。
采用六基因组合高效重编程 aMSCs 为 ra-βCs。ra-βCs 和 aMSCs 的共移植作为治疗犬糖尿病的方法是可行的，为犬糖尿病的治疗提供了理论依据和治疗方法。
