Researchers at Wenzhou Medical University have discovered a groundbreaking approach to treating type 1 diabetes—using the spleen as a novel site for islet transplantation. This method restores long-term glycemic control without the need for full immunosuppression, offering a promising alternative to traditional liver-based techniques.
The Problem with Liver-Based Transplantation
In type 1 diabetes, the immune system targets and destroys insulin-producing beta cells located in the pancreatic islets of Langerhans. Islet transplantation traditionally involves transferring these clusters into the liver via the portal vein. Once engrafted, the islets resume insulin production to stabilize blood sugar levels.
However, the liver environment presents major challenges. Low oxygen levels, immune attacks, and the stiffness of hepatic tissue lead to rapid cell death. In fact, more than 70% of transplanted islets are lost before they can engraft, often requiring multiple donors per recipient and limiting clinical success.
Exploring Alternative Transplantation Sites
Over the years, scientists have tested several alternate transplant locations, including the eye, omentum, and skeletal muscle. Unfortunately, each option introduces its own set of complications—such as invasive procedures, poor islet survival, or irregular insulin delivery.
A Novel Approach: Spleen Remodeling with Nanoparticles
To overcome these obstacles, researchers engineered the spleen to serve as a supportive transplant site. As per Medical Xpress, they utilized glucomannan-coated silica nanoparticles to remodel spleen tissue, enhancing both vascularization and local immune tolerance.
In the study, titled “Islet transplantation in immunomodulatory nanoparticle–remodeled spleens,” published in Science Translational Medicine, the team tested this strategy on diabetic mice and cynomolgus macaques. Diabetic conditions were induced using streptozotocin, and spleen remodeling was guided by B-ultrasound.
Step-by-Step Transplant Procedure
Researchers injected nanoparticles into the spleens of mice and macaques to reshape tissue and suppress immune responses. In mice, four injections were administered over two weeks, following surgical relocation of the spleen to an extraperitoneal site. In macaques, weekly injections targeted the upper, middle, and lower splenic poles over four weeks.
Islets from mouse, rat, and human donors were prepared using collagenase digestion and density-gradient purification. The team transplanted these islets directly into the remodeledspleens and monitored outcomes through blood glucose tracking, insulin and C-peptide assays, and glucose tolerance tests.
Strong Graft Survival and Vascular Integration
Results showed impressive graft viability. In mice, both mouse and rat islets survived for at least 90 days, maintaining normal endocrine structure. Without spleen remodeling, grafts were rejected within a week.
The remodeled spleens supported rapid blood vessel growth, with dense vascular networks forming within two weeks. In macaques, human islets remained intact for at least 28 days and showed strong revascularization without structural damage.
Immunological Tolerance in Remodeled Spleens
Nanoparticle treatment significantly altered the spleen’s immune environment. In mice, it promoted the expansion of regulatory T cells and M2 macrophages while suppressing inflammatory responses. Minimal antibody production and cytokine activity occurred, even across species barriers.
Similarly, macaques exhibited increased anti-inflammatory gene expression and reduced T cell activation. Laboratory tests confirmed that the nanoparticles inhibited T cell proliferation and directed macrophages toward a regulatory phenotype.
Effective Restoration of Glycemic Control
Transplanted islets quickly restored normal blood sugar in diabetic mice. Normoglycemia was achieved within days and sustained for 90 days. Glucose tolerance and insulin secretion mirrored healthy controls.
In macaques, human islet grafts maintained insulin and C-peptide secretion for at least 28 days. Glycemic control remained stable under reduced immunosuppression. Notably, removing the spleen reversed the therapeutic effects, confirming the functional role of the grafts.
A Step Toward Clinical Application
The researchers concluded that spleen-based islet transplantation presents a viable and less invasive alternative to liver-based approaches. By creating an engineered microenvironment that supports both immune tolerance and vascular integration, this technique significantly reduces the need for intense immunosuppressive therapy.
While longer-term studies and human trials are necessary, this method shows strong potential for advancing islet-based treatments for type 1 diabetes and making them more accessible in clinical practice.