The generation of effective insulin-producing cells from ADSC derived from type 1 diabetes mellitus patients

Background & Aim We have reported the possibility of non-clinical PoC for generating insulin-producing cells (IPCs) differentiated from adipose-derived stem cells (ADSCs). However, whether ADSC isolated from type 1 diabetes mellitus (T1DM) patients has the differentiation ability or not is still unclear. Thus, we aimed to determine whether appropriately responsive IPCs could be generated from ADSCs isolated from actual T1DM patients. Methods, Results & Conclusion Methods We isolated ADSCs from the discarded adipose tissue from four patients undergoing surgery at our institute and differentiated them into IPCs using our established two-step xeno-antigen free, three-dimensional culture method (UMIN000035546,IRB approved on Jan 10, 2018). Characters of isolated ADSCs, in vitro cell quality and cell function, programmed cell death ligand-1(PDL-1) expression and in vivo functional tests by transplantation to streptozotocin (STZ) induced diabetic nude mice were investigated. Results ADSCs from T1DM patients and commercially obtained ADSCs showed the same surface markers; CD31−CD34−CD45−CD90+CD105+CD146−. Moreover, the generated IPCs at day 21 demonstrated appropriate autonomous insulin secretion in vitro (stimulation index;3.5). The non-fasting blood glucose concentrations of STZ-induced diabetic nude mice were normal 30 days after IPC transplantation. The normalized rate of STZ-induced diabetic nude mice was significantly different to the sham-operated group (P Conclusions These findings suggest that IPCs obtained from the adipose tissue of T1DM patients are capable of secreting insulin long-term and achieving normoglycemia following a single auto-transplantation, and without the need for immunosuppression.