Human islets grown in the immune-remodeled spleen of macaques. Credit: Lei Dong/Nanjing University and Jian Xiao/Wenzhou Medical University

Wenzhou Medical University researchers have reimagined the spleen as a viable site for islet transplantation, enabling long-term diabetes control without the burden of full immunosuppression. Nanoparticle-driven spleen remodeling allowed transplanted mouse, rat, and human islets to restore normal blood sugar in diabetic rodents and cynomolgus macaques.

In type 1 diabetes, the immune system destroys native beta cells, the insulin-producing cells housed within pancreatic clusters called islets of Langerhans. Islet transplantation transfers these clusters from donor pancreases into the portal vein of the recipient's liver, where they settle in the hepatic microvasculature. Once in place, they resume insulin secretion to reduce or eliminate injections and restore glycemic control.

Liver-based transplantation has significant drawbacks. Immune attack, low oxygen tension, and the rigidity of hepatic tissue often destroy most transplanted islets within hours. Upward of 70% of cells are destroyed before engraftment, forcing reliance on multiple donors per recipient and blunting therapeutic success.

Alternate sites such as the eye, omentum, and striated muscle have been explored, yet each introduces complications ranging from invasive surgery to poor islet survival or abnormal insulin delivery patterns.

In the study, "Islet transplantation in immunomodulatory nanoparticle–remodeled spleens, " published in Science Translational Medicine, researchers engineered spleens with glucomannan-coated silica nanoparticles to create a vascularized, immunosuppressive environment for transplanted islets.

Thyroid restoration with vascular network in the spleen. Credit: Lei Dong/Nanjing University

Researchers tested the transplantation strategy in mice and cynomolgus macaques. Murine models received either mouse or rat islets, while macaques were implanted with human islets from two donors. Diabetic conditions were induced using streptozotocin in both species. In macaques, nanoparticle injection and transplantation were guided by B-ultrasound and followed by tailored immunosuppressive regimens.

Konjac glucomannan–coated silica nanoparticles were injected into the spleens of mice and macaques to remodel tissue architecture and modulate local immunity.

In mice, the procedure involved four injections of nanoparticles over two weeks following surgical translocation of the spleen to an extraperitoneal site. In macaques, nanoparticles were delivered weekly for four weeks under ultrasound guidance into the upper, middle, and lower splenic poles.

Islet grafts were prepared from mouse, rat, or human pancreases using collagenase digestion and density-gradient purification. Mouse and rat islets were transplanted directly into remodeled spleens in diabetic mice.

Human islets were injected into macaque spleens under ultrasound guidance and supported with immunosuppression adjusted for the experimental group. Glycemic status was tracked by serial blood glucose measurements, insulin and C-peptide assays, and glucose tolerance testing.

Islets transplanted into remodeled spleens formed stable, long-lasting grafts. In diabetic mice, both mouse and rat islets survived for 90 days and maintained typical endocrine structure. Without remodeling, grafts were lost within a week.

Rapid vascular integration supported graft survival. Blood vessels infiltrated grafts within days, and dense vascular networks formed within two weeks. In macaques, human islets remained intact for at least 28 days and showed clear revascularization without structural complications.

Mouse spleen transformed into a liver. Credit: Lei Dong/Nanjing University, Science Advances, 2020, DOI: 10.1126/sciadv.aaz9974.

Remodeled spleens developed a local immune environment that supported graft tolerance. In mice, nanoparticle treatment expanded regulatory T cells and M2 macrophages while reducing effector T cells and pro-inflammatory cytokines. Grafted islets triggered minimal antibody or cytokine responses, even across species barriers.

In macaques, remodeled spleens showed similar immune remodeling, with anti-inflammatory gene expression and dampened T cell activation. In vitro tests confirmed that nanoparticles suppressed T cell proliferation and promoted macrophage polarization toward a regulatory phenotype.

Transplanted islets in remodeled spleens rapidly restored blood glucose control in diabetic mice. Normoglycemia was achieved within days and maintained for up to 90 days with both mouse and rat islets. Glucose tolerance and insulin secretion matched those of healthy controls.

In macaques, human islet grafts sustained insulin and C-peptide release for at least 28 days. Glycemic stability was maintained under reduced immunosuppression, and splenectomy reversed the effect, confirming graft-dependent function.

Researchers concluded that spleen remodeling offers a viable alternative to liver-based islet transplantation. The engineered microenvironment supported islet survival and function across species with reduced immune intervention.

The approach offers a less invasive, more reliable, less risky method for restoring insulin production in type 1 diabetes. While longer-term studies and clinical trials are still required, initial results look promising as a strategy that could bring islet-based therapies closer to routine clinical use.

More information: Mi Liu et al, Islet transplantation in immunomodulatory nanoparticle–remodeled spleens, Science Translational Medicine (2025). DOI: 10.1126/scitranslmed.adj9615  Journal information: Science Translational Medicine, Science Advances

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