Shusen Wang ∙ Yuanyuan Du∙ Boya Zhang∙ Shuang Wang ∙ Hongkui Deng ∙ Zhongyang Shen

Cell. 2024 Oct 31;187(22):6152-6164.e18.
DOI: 10.1016/j.cell.2024.09.004.

Highlights
Sub-anterior rectus sheath Insulin requirement (Units/day) d Patient-derived islets were generated with chemically induced pluripotent stem cells d Transplantation of these islets to an abdominal site led to engraftment in one patient d Exogenous insulin-independent glycemic control was restored in the patient d All safety and efficacy clinical endpoints were met at 1-year follow-up of the patient.

SUMMARY
We report the 1-year results from one patient as the preliminary analysis of a first-in-human phase I clinical trial (ChiCTR2300072200) assessing the feasibility of autologous transplantation of chemically induced pluripotent stem-cell-derived islets (CiPSC islets) beneath the abdominal anterior rectus sheath for type 1 diabetes treatment. The patient achieved sustained insulin independence starting 75 days post-transplantation. The patient’s time-in-target glycemic range increased from a baseline value of 43.18% to 96.21% by month 4 post-transplantation, accompanied by a decrease in glycated hemoglobin, an indicator of long term systemic glucose levels at a non-diabetic level. Thereafter, the patient presented a state of stable glycemic control, with time-in-target glycemic range at >98% and glycated hemoglobin ataround5%. At1year, the clinical data met all study endpoints with no indication of transplant-related abnormalities. Promising re sults from this patient suggest that further clinical studies assessing CiPSC-islet transplantation in type 1diabetes are warranted.