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

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.

Causal relationship between nonalcoholic fatty liver disease and different sleep traits: a bidirectional Mendelian randomized study

“…For example, FTO expression is increased in NAFLD, and it promotes hepatic steatosis by targeting PPARa (61). Its upregulation can reduce insulin secretion via the inflammatory NF-kB pathway and disrupts lipid utilization in skeletal muscles by suppressing the PPARb/dand AMPK pathways, leading to the occurrence of diabetic hyperlipidemia (62).A recently research found that RFX3 is a novel functional genes that regulate the development of adipose mesenchymal stem cells into islet b-cells (63). KSR2 plays an important role in energy metabolism.…”

Multiomics analysis of platelet-rich plasma promoting biological performance of mesenchymal stem cells

“…The lab preserved frozen P3 generation cADMSCs were resuscitated using FBS medium. The isolation, culture and identification of the cells are shown in the previous results [ 14 , 15 ], and after the cells were attached to the wall, the medium was abandoned, and the cells were cultured through the above medium, respectively, to observe the growth rate and growth morphology of the cells. At the same time, cells were tested for proliferation according to the instructions of Cell Counting Kit-8 (Sigma‒Aldrich, 96992-500TESTS-F, USA).…”

Immunomodulatory Mechanisms and Therapeutic Potential of Mesenchymal Stem Cells

“…MSCs restore mucosal immunity and rejuvenate mucosal immunosenescence in the elderly [ 22 ]. Moreover, reprogramming AMSCs into islet β-cells (reprogrammed AMSCs-derived islet β-cells) with low immunogenicity achieved ideal therapeutic effects in treating canine diabetes mellitus [ 23 ].…”