title: Combinatorial Treatment of Bone Marrow Transplantation and Regulatory T Cells Improves Glycemia in Streptozotocin-diabetic Mice.
abstract: Autologous hematopoietic stem cell transplantation (HSCT) has limited benefits in patients with a long-duration of diabetes. To test whether a T regulatory cells (Tregs) and syngeneic bone marrow transplantation (syn-BMT) co-transplantation regimen will be effective, BMT±Tregs infusion was performed in streptozotocin-diabetic mice with a long-duaration of diabetes. Diabetic status, pancreata morphometry and Tregs/Th17 balancing were tested on day 100 after transplantation. While hyperglycemia relapsed in mice receiving BMT monotherapy about 6 weeks after transplantation, combined therapy with BMT+Tregs improved hyperglycemia and C-peptides, preserved islet cell mass within 100 days after BMT. Although both groups BMT and BMT+Tregs induced Tregs/Th17 rebalancing, combined treatment of BMT+Tregs synergistically elevated TGF-β1 and FoxP3 expression compared with BMT monotherapy. The sustained rebalance of Tregs/Th17 may be one possible explanation for the longer benefits of the combined treatment of BMT+Tregs over BMT monotherapy to mice with a long-duaration of diabetes. This observation of the therapeutic potential of BMCs+Tregs treatment may have important implications for clinical therapy for patients with a long-duration of diabetes.
authors.affiliation: Center of Translational Medicine, Jiangsu Key Laboratory of Molecular Medicine, Nanjing University Medical School, China.
authors.forename: H
authors.initials: H
authors.lastname: Min
authors.affiliation: Department of Respiratory Medicine, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China.
authors.forename: J
authors.initials: J
authors.lastname: Ding
authors.affiliation: Center of Translational Medicine, Jiangsu Key Laboratory of Molecular Medicine, Nanjing University Medical School, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Wen
authors.affiliation: Center of Translational Medicine, Jiangsu Key Laboratory of Molecular Medicine, Nanjing University Medical School, China.
authors.forename: X
authors.initials: X
authors.lastname: Ma
authors.affiliation: Center of Translational Medicine, Jiangsu Key Laboratory of Molecular Medicine, Nanjing University Medical School, China.
authors.forename: Q
authors.initials: Q
authors.lastname: Gao
mesh_terms: D000818:Animals; D016026:Bone Marrow Transplantation; D003921:Diabetes Mellitus, Experimental / Q000276:immunology / Q000628:therapy*; D051858:Forkhead Transcription Factors / Q000276:immunology; D005786:Gene Expression Regulation / Q000276:immunology; D008297:Male; D051379:Mice; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000637:transplantation*; D058504:Th17 Cells / Q000276:immunology; D053773:Transforming Growth Factor beta1 / Q000276:immunology; D014185:Transplantation, Isogeneic
chemical_list: D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; C508961:Tgfb1 protein, mouse; D053773:Transforming Growth Factor beta1