First-Trimester Human Fetal Pancreas Transplantation for Type 1 Diabetes Treatment
An Alternative Approach for Achieving Long-Term Graft Survival?
- From the La Jolla Institute for Allergy and Immunology, La Jolla, California
- Address correspondence and reprint requests to Matthias von Herrath, La Jolla Institute for Allergy and Immunology, 9420 Athena Circle, La Jolla, CA 92037. E-mail:
- MHC, major histocompatibility complex
- PBMC, peripheral blood mononuclear cell
- Treg, regulatory T-cell
Type 1 diabetes results from immune-mediated destruction of insulin-producing β-cells of the pancreas. The disease manifests itself symptomatically when the resident β-cells become unable to maintain normoglycemia. In human insulitis, mainly CD8 lymphocytes and B-cells, but also CD4 cells and activated antigen-presenting cells (APCs), are found (1–3). Strikingly, strong upregulation of MHC class I molecules and type 1 interferons have also been observed in noninfiltrated islets from human type 1 diabetic patients, making the involvement of a viral β-cell infection a feasible scenario in terms of disease pathogenesis (4). Among treatments that are currently being evaluated for stable reversal of type 1 diabetes, pancreas or islet transplantation holds promise, since it provides already diabetic patients with new functional β-cells. The routine clinical use of pancreas or isolated intrahepatic islet transplantation is, however, hampered predominantly by the lack of sufficient donor tissue. In addition, islets injected into the portal vein are often lost after 4–5 years, even under optimized immunosuppressive regimens (5), which renders whole pancreas or combined pancreas-kidney transplants important therapeutic alternatives (6).
With this setting, human fetal pancreas derived from therapeutic termination of pregnancies as an alternative source of β-cells has increasingly become an attractive alternative. Potential advantages include its greater proliferative capacity and maturation potential in vivo, as …