Bone Marrow Transplantation Induces Normoglycemia in a Type 2 Diabetes Mellitus Murine Model

Objective. To study the cellular mechanisms involved in the regression of diabetic nephropathy, bone marrow-derived cells must be identified. The aim of this study was to obtain a diabetic chimeric model with bone marrow cells expressing enhanced green fluorecence protein (EGFP), without modifying the course of diabetic nephropathy. Materials and Methods. Bone marrow transplantation (BMT) was performed in an obese type 2 diabetic murine model (db/db) owing to a mutation in the leptin receptor gene. Whole bone marrow from female donor C57BL/6 EGFP+ mice was transplanted into 8-week-old C57BL/6 mice and into 8- and 24-week-old female C57BLKS (db/db) EGFP- mice. Recipient mice received total body irradiation (TBI) followed by bone marrow (BM) cell infusion. We tested various irradiation doses (Gy) and numbers of BM cells. Results. When a low TBI dose and a small number of BM cells were administered, only syngeneic C57BL/6 mice became chimeric, whereas allogeneic db/db mice showed rejection. When Gy dose and BM cells were increased, db/db mice became chimeric. However, 8-week-old db/db mice lost the obese phenotype and became normoglycemic, probably due to peripheral BM cell infiltration. Conversely, 24-week-old db/db mice remained obese showing similar blood glucose values, body weights, albuminuria, and glomerular lesions at nontransplanted db/db mice. Conclusions. Recipient age greatly influenced the peripheral repopulation after BMT in db/db mice. Only the adult chimeric db/db mice seemed to be a good model to study the cellular mechanisms involved in the regression of diabetic nephropathy.