Novel subcutaneous islet transplantation method using a bioabsorbable medical device to facilitate the guidance of the highly vascularized transplantation site

Introduction: Stem cell-derived β-like cells have recently garnered considerable attention as a potential solution to donor shortage. However, conventional intra-portal transplantation poses difficulties due to the impossibility of biopsy or removing the graft site, making subcutaneous islet transplantation a more viable alternative. The lack of blood flow and scaffolding for cell adhesion has significantly restricted the viability and function of transplanted cells, thus presenting a major challenge for the subcutaneous transplantation. In this study, we aimed to investigate the potential of a novel subcutaneous islet transplantation method using a bioabsorbable medical device and basic fibroblast growth factor, which provides blood flow and a scaffold for the transplanted islets, in overcoming these limitations. Methods: We performed experiments in a syngeneic transplantation using C57BL/6 mice. Collagen-containing bioabsorbable devices comprising basic fibroblast growth factor at a concentration of 16 µg/cm2 were subcutaneously implanted into a drug-induced C57BL/6 mouse model of diabetes to induce the formation of vascular beds. At 14 days post-implantation, we transplanted 200 syngeneic islets and evaluated cell viability and function. As a comparison, we also performed intra-portal transplantation, subcutaneous transplantation without a device, and subcutaneous transplantation using agarose as a non-absorbable device. Results: The bioabsorbable device group did not require device removal at the time of transplantation, which simplified the procedure. In the no device subcutaneous transplantation group, none of mice reached normal serum glucose level. In the bioabsorbable device group (n=16), the proportions of mice with normalization of serum glucose levels were 50% at 30 days, and 94% at 100 days post transplantation. The median time to normalization of glucose levels was 33 days (15–73 days). Elevation of serum glucose levels was observed at the time of graft removal in all mice, and islets forming clusters were detected in the tissue samples of the grafts, indicating that the engraftment of islets was successful. The proportions of mice with normalization of serum glucose levels in the bioabsorbable device group were comparable to those in the intra-portal transplantation and the non-absorbable device groups. Conclusion: Our study demonstrates the potential of a bioabsorbable device that can provide a scaffold and induce vascular bed formation prior to subcutaneous islet transplantation in a mouse model of drug-induced diabetes.