Stanford Medicine researchers reported that a combined transplant procedure cured or prevented autoimmune Type 1 diabetes in mice by creating a hybrid immune system through simultaneous transplantation of donor hematopoietic (blood) stem cells and insulin-producing pancreatic islet cells from immunologically mismatched donors.

The protocol used a milder pre-transplant conditioning regimen than conventional bone marrow transplants. That regimen included immune‑targeting antibodies, low‑dose radiation, and an added autoimmune‑disease drug to reduce recipient marrow enough to permit donor blood‑stem‑cell engraftment without high‑dose chemotherapy or full‑myeloablative radiation. The engrafted donor stem cells coexisted with recipient immune cells, producing partial donor–recipient immune chimerism (a mixed-origin, or “hybrid,” immune system) that tolerated the transplanted islets and halted autoimmune destruction of insulin-producing cells. Treated animals did not develop graft‑versus‑host disease in the experiments reported.

In prevention experiments, the regimen prevented development of Type 1 diabetes in 19 of 19 autoimmune‑prone mice. In reversal experiments, it reversed longstanding autoimmune diabetes in 9 of 9 mice. None of the animals that were cured required ongoing insulin injections or immunosuppressive drugs for the six‑month duration of the experiments.

The investigators noted practical challenges for translating the approach to humans. Human pancreatic islet cells are currently obtainable mainly from deceased donors, and it is uncertain whether islets from a single donor would provide sufficient cell mass to reverse established disease in people. Potential solutions under consideration include generating islet cells from pluripotent human stem cells or developing methods to improve survival and function of transplanted islets. The researchers also suggested the milder conditioning plus hybrid immune approach could, in principle, be explored for other autoimmune diseases, for some noncancerous blood disorders, or to increase durability of mismatched solid‑organ transplants without lifelong immunosuppression.

The study was published in the Journal of Clinical Investigation and was funded by multiple National Institutes of Health grants, Stanford research centers, and private foundations. The authors cautioned that results in mice do not automatically translate to humans and that further research is required.

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