PROLONGED SURVIVAL OF NEONATAL PORCINE ISLET XENOGRAFTS IN MICE TREATED WITH A DONOR-SPECIFIC TRANSFUSION AND ANTI-CD154 ANTIBODY1
| Autor: | Michael C. Appel, Dale L. Greiner, Aldo A. Rossini, Scott J. Banuelos, John P. Mordes, Leonard D. Shultz |
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| Rok vydání: | 2004 |
| Předmět: |
Transplantation
geography CD40 geography.geographical_feature_category Combination therapy biology business.industry medicine.medical_treatment Spleen Immunosuppression Islet medicine.disease Andrology medicine.anatomical_structure Diabetes mellitus Immunology medicine biology.protein CD154 business |
| Zdroj: | Transplantation. 77:1341-1349 |
| ISSN: | 0041-1337 |
| Popis: | Background Combined treatment with a single donor-specific transfusion (DST) and a brief course of anti-mouse CD154 monoclonal antibody (mAb) to induce co-stimulation blockade leads to long-term murine islet allograft survival. The authors hypothesized that this protocol could also induce long-term survival of neonatal porcine islet cell clusters (NPCC) in chemically diabetic immunocompetent mice and allow their differentiation into functional insulin-producing cells. Methods. Pancreata from 1- to 3-day-old pigs were collagenase digested and cultured for 8 days. NPCC were recovered and transplanted into the renal subeapsular space. Recipients included chemically diabetic nonobese diabetic (NOD)-scid and C57BL/6 mice that were otherwise untreated, treated with anti-CD154 mAb alone, or treated with DST plus anti-CD154 mAb. Plasma glucose concentration and body weight were measured, and xenografts were examined histologically. Results. NPCC fully differentiated and restored normoglycemia in four of five diabetic NOD-scid recipients but were uniformly rejected by diabetic C57BL/6 recipients. Anti-CD154 mAb monotherapy restored normoglycemia in 4 of 10 (40%) NPCC-engrafted, chemically diabetic C57BL/6 mice, but combined treatment with DST and anti-CD154 mAb restored normoglycemia in 12 of 13 (92%) recipients. Reversal of diabetes required 5 to 12 weeks. Surviving grafts were essentially free of inflammatory infiltrates 15 weeks after transplantation. Conclusions. Combination therapy with a single DST and a brief course of anti-mouse CD154 mAb without maintenance immunosuppression permits survival and differentiation of NPCC in diabetic C57BL/6 mice. Successful grafts were associated with durable restoration of normoglycemia and the absence of graft inflammation. |
| Databáze: | OpenAIRE |
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