title: Chimeric Allografts Induced by Short-Term Treatment With Stem Cell-Mobilizing Agents Result in Long-Term Kidney Transplant Survival Without Immunosuppression: A Study in Rats.
abstract: Transplant tolerance allowing the elimination of lifelong immunosuppression has been the goal of research for 60 years. The induction of mixed chimerism has shown promise and has been extended successfully to large animals and to the clinic; however, it remains cumbersome and requires heavy early immunosuppression. In this study, we reported that four injections of AMD3100, a CXCR4 antagonist, plus eight injections of low-dose FK506 (0.05 mg/kg per day) in the first week after kidney transplantation extended survival, but death from renal failure occurred at 30-90 days. Repeating the same course of AMD3100 and FK506 at 1, 2 and 3 mo after transplant resulted in 92% allograft acceptance (n = 12) at 7 mo, normal kidney function and histology with no further treatment. Transplant acceptance was associated with the influx of host stem cells, resulting in a hybrid kidney and a modulated host immune response. Confirmation of these results could initiate a paradigm shift in posttransplant therapy.
authors.affiliation: Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD.|Department of Urology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China.
authors.forename: X
authors.initials: X
authors.lastname: Hu
authors.affiliation: Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD.|Department of Surgery, Kochi Health Center, Kochi University, Kochi, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Okabayashi
authors.affiliation: Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD.
authors.forename: A M
authors.initials: AM
authors.lastname: Cameron
authors.affiliation: Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD.
authors.forename: Y
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD.|Department of Surgery, Tokyo Medical University, Tokyo, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Hisada
authors.affiliation: Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD.
authors.forename: J
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD.
authors.forename: L C
authors.initials: LC
authors.lastname: Raccusen
authors.affiliation: Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD.
authors.forename: Q
authors.initials: Q
authors.lastname: Zheng
authors.affiliation: Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD.
authors.forename: R A
authors.initials: RA
authors.lastname: Montgomery
authors.affiliation: Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD.
authors.forename: G M
authors.initials: GM
authors.lastname: Williams
authors.affiliation: Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD.
authors.forename: Z
authors.initials: Z
authors.lastname: Sun
mesh_terms: D064591:Allografts; D000818:Animals; D030801:Animals, Genetically Modified; D019380:Anti-HIV Agents / Q000494:pharmacology; D001596:Benzylamines; D065095:Calcineurin Inhibitors / Q000494:pharmacology; D000080027:Cyclams; D005919:Glomerular Filtration Rate; D006084:Graft Rejection / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D006085:Graft Survival / Q000276:immunology; D019650:Hematopoietic Stem Cell Mobilization; D006571:Heterocyclic Compounds / Q000494:pharmacology*; D007676:Kidney Failure, Chronic / Q000601:surgery; D007677:Kidney Function Tests; D016030:Kidney Transplantation / Q000009:adverse effects*; D036102:Peripheral Blood Stem Cell Transplantation; D051381:Rats; D011917:Rats, Inbred Lew; D016559:Tacrolimus / Q000494:pharmacology*; D018183:Transplantation Chimera; D023001:Transplantation Tolerance / Q000276:immunology*
chemical_list: D019380:Anti-HIV Agents; D001596:Benzylamines; D065095:Calcineurin Inhibitors; D000080027:Cyclams; D006571:Heterocyclic Compounds; C088327:plerixafor; D016559:Tacrolimus
keywords: basic (laboratory) research/science; kidney transplantation/nephrology; organ acceptance; pathology/histopathology; regenerative medicine; rejection: acute; stem cells; tissue injury and repair; tolerance; translational research/science