Reprogramming adipose mesenchymal stem cells into islet β-cells for the treatment of canine diabetes mellitus

Author:

Dai Pengxiu,Qi Guixiang,Xu Haojie,Zhu Mingde,Li Jiakai,Chen Yijing,Zhang Luwen,Zhang Xinke,Zhang YihuaORCID

Abstract

Abstract Background 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. Methods 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. Results 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. Conclusions 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.

Funder

National Natural Science Foundation of China

Natural Science Foundation of Shaanxi Province

Program of Shaanxi Province Science and Technology Innovation Team

Publisher

Springer Science and Business Media LLC

Subject

Cell Biology,Biochemistry, Genetics and Molecular Biology (miscellaneous),Molecular Medicine,Medicine (miscellaneous)

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