Subcutaneous device-free islet transplantation

Abstract

Diabetes mellitus is a chronic metabolic disease, characterized by high blood sugar levels; it affects more than 500 million individuals worldwide. Type 1 diabetes mellitus (T1DM) is results from insufficient insulin secretion by islets; its treatment requires lifelong use of insulin injections, which leads to a large economic burden on patients. Islet transplantation may be a promising effective treatment for T1DM. Clinically, this process currently involves directly infusing islet cells into the hepatic portal vein; however, transplantation at this site often elicits immediate blood-mediated inflammatory and acute immune responses. Subcutaneous islet transplantation is an attractive alternative to islet transplantation because it is simpler, demonstrates lower surgical complication risks, and enables graft monitoring and removal. In this article, we review the current methods of subcutaneous device-free islet transplantation. Recent subcutaneous islet transplantation techniques with high success rate have involved the use of bioengineering technology and biomaterial cotransplantation—including cell and cell growth factor co-transplantation and hydrogel– or simulated extracellular matrix–wrapped subcutaneous co-transplantation. In general, current subcutaneous device-free islet transplantation modalities can simplify the surgical process and improve the posttransplantation graft survival rate, thus aiding effective T1DM management.

Novel Treatment Modalities of Type 1 Diabetes Mellitus: Opportunities and Challenges

“…Moreover, uncertainties surround the effectiveness and safety of biomaterials used to encapsulate artificial islets created from stem cells, with concerns about post-implantation transdifferentiation, teratoma formation, or graft migration requiring careful consideration. To enhance the long-term efficacy and safety of islet cell treatment for diabetes patients, efforts must concentrate on improving islet graft survival and functionality in highly vascularized, nutrient-and oxygen-rich environments [56].…”

Strategy for Clinical Setting of Co-transplantation of Mesenchymal Stem Cells and Pancreatic Islets

“…Subcutaneous transplantation of islets is simple and easy to monitor and poses low complication risk 86 . However, the lack of vascularization in the subcutaneous space hinders the supply of nutrients and oxygen, influencing the effect of grafts.…”

“…The results indicated that both the BMSC–islet and EMSC–islet composites significantly reduced fragmentation and increased islet mass in porcine pancreatic islets alone. Finally, in a prevascularized deviceless (DL) subcutaneous transplantation method, ADMSCs and islet cells were colocalized in the subcutaneous spaces 86 . The DL subcutaneous space was prepared by implanting a nylon catheter under the skin of mice and then transplanting islets and ADMSCs that had been co-cultured for 24 h into the DL subcutaneous space or renal capsule, which demonstrated that DL subcutaneous space in combination with ADMSCs achieved euglycemia 11 weeks after transplantation but prevented deleterious graft fibrosis overgrowth 89 .…”