*Purpose: Previous first-in-human pilot study showed safety but the conditions did not allow for detectable islet function post-transplantation into the pre-vascularized Sernova Cell Pouches (SCPs) implanted subcutaneously. Herein, in the current Phase I/II study we tested clinically, islet engraftment in modified conditions after transplantation into the SCP.

*Methods: First, SCPs were implanted below the anterior rectus sheath in type 1 diabetes patients with severe hypoglycemia unawareness and no stimulated C-peptide. Three weeks later Thymoglobulin, tacrolimus, and mycophenolate were initiated. During the infusion, islets were suspended in the patient’s own serum instead of saline to provide an optimal microenviroment for engraftment. Islets with purity over 90% were transplanted. A sentinel pouch was excised for evaluation 3 months after each transplant. Islet graft function was monitored based on glucose control, C-peptide and insulin usage.

*Results: Early in the ongoing study, wound infection required SCP excision in one of six SCP implanted individuals. The two furthest advanced patients received two subsequent islet transplants into the SCPs resulting in persistent islet graft function (positive serum C-peptide). Peak serum C-peptide remains currently at a level of 0.4-0.48 ng/ml, at 6 and 3 months after the second transplant in first and second patient, respectively. Islet engraftment was 9-fold higher when the islet mass was reduced by half to 3,300IEQ/kg (0.8 ml of tissue) during the second transplant in both patients. In the first patient, glucose control improved as A1c decreased from 6.3 to 6.0, insulin requirements dropped by 23% and CGM Time Below Range (TBR) dropped from 12% to 5%. In the second patient A1c dropped from 10.3 to 7.6, insulin requirements dropped by 40% and Time Above Range dropped from 76% to 48%. None of the patients experienced severe hypoglycemic episodes after the second islet transplant. Of note, both patients lost initially 7-15% of body weight and maintained stable weight afterwards. Preserved islet anatomy and endocrine function were found on histopathological evaluation of the vascularized environment within excised sentinel pouches.

*Conclusions: Modified conditions resulted in persistent islet graft function after SCP transplantation. Limiting islet mass to 3,000IEQ/kg per transplant significantly improved islet engraftment into Sernova Cell Pouches.

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