Innovative Spleen-Based Islet Transplantation Enables Long-Term Diabetes Management Without Full Immunosuppression

Recent advancements in diabetes treatment have introduced a pioneering approach that redefines islet transplantation by utilizing the spleen as a transplantation site. Researchers from Wenzhou Medical University have developed a method where the spleen is transformed into a supportive environment for insulin-producing islets, using nanoparticles to remodel tissue and modulate local immunity.

In type 1 diabetes, the immune system attacks pancreatic beta cells within islets of Langerhans, leading to insulin deficiency. Traditional islet transplantation involves transferring these cells into the liver via the portal vein, but this method faces significant challenges. The hepatic environment often poses hostile conditions—such as low oxygen levels and immune attacks—that result in the destruction of transplanted islets within hours, forcing the use of multiple donors and limiting therapeutic success.

To address these issues, the new strategy involves nanoparticle-driven spleen remodeling. Specifically, glucomannan-coated silica nanoparticles are injected into the spleen to promote vascularization and create an immunosuppressive microenvironment. This remodeled spleen supports the long-term survival of transplanted islets from mice, rats, and humans.

Experimental procedures included transplanting mouse and rat islets directly into the remodeled spleen of diabetic mice, which sustained graft viability for over 90 days. Human islets transplanted into macaques' spleens remained functional for at least 28 days, demonstrating effective revascularization and minimal structural complications. The remodeling process also modifies the spleen's immune landscape, expanding regulatory T cells and M2 macrophages while suppressing effector T cells and inflammatory cytokines, thereby promoting graft tolerance.

Blood glucose levels normalized swiftly in treated mice, maintaining stability for three months, with insulin secretion comparable to healthy controls. Similarly, in macaques, human islet transplants produced persistent insulin and C-peptide secretion, with glycemic stability maintained under reduced immunosuppression. Reversing the graft effect through splenectomy confirmed the functional dependence on the transplanted islets.

This innovative approach offers several advantages over conventional liver-based transplants. It reduces reliance on extensive immunosuppression, minimizes invasive procedures, and enhances graft survival by fostering a supportive immune environment. While longer-term studies and clinical trials are essential, these promising results suggest that spleen remodeling could become a viable, less invasive alternative for islet transplantation in diabetes therapy.

Source: [https://medicalxpress.com/news/2025-05-spleen-based-islet-transplantation-glycemic.html]