title: Chimeric Allografts Induced by Short-Term Treatment With Stem Cell Mobilizing Agents Result in Long-Term Kidney Transplant Survival Without Immunosuppression: II, Study in Miniature Swine.
abstract: Transplantation is now lifesaving therapy for patients with end-stage organ failure but requires lifelong immunosuppression with resultant morbidity. Current immunosuppressive strategies inhibit T cell activation and prevent donor-recipient engagement. Therefore, it is not surprising that few host cells are demonstrated in donor grafts. However, our recent small animal studies found large numbers of recipient stem cells present after transplantation and pharmacological mobilization, resulting in a chimeric, repopulated organ. We now confirm these findings in a well-characterized large animal preclinical model. Here, we show that AMD3100 and FK506 mobilization of endogenous stem cells immediately post kidney transplantation combined with repeat therapy at 1, 2, and 3 months led to drug-free long-term survival in maximally immunologically mismatched swine. Three long-term recipients have stable chimeric transplants, preserved antidonor skin graft responses, and normal serum creatinine levels despite withdrawal of all medication for 3 years.
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: R N
authors.initials: RN
authors.lastname: Wesson
authors.affiliation: Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD.
authors.forename: A R
authors.initials: AR
authors.lastname: Ahmadi
authors.affiliation: Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD.|Transplant Center, Mayo Clinic, Phoenix, AZ, USA.
authors.forename: A L
authors.initials: AL
authors.lastname: Singer
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: 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: Shigoka
authors.affiliation: Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD.|Transplant Center, Tianjin First Central Hospital, Tianjin, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Fu
authors.affiliation: Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD.|Transplant Center, Tianjin First Central Hospital, Tianjin, China.
authors.forename: W
authors.initials: W
authors.lastname: Gao
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 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; D019380:Anti-HIV Agents / Q000494:pharmacology; D001596:Benzylamines; D065095:Calcineurin Inhibitors / Q000494:pharmacology; D000080027:Cyclams; 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; D016030:Kidney Transplantation / Q000009:adverse effects*; D036102:Peripheral Blood Stem Cell Transplantation; D016038:Skin Transplantation; D013552:Swine; D013556:Swine, Miniature; 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: animal models: porcine; basic (laboratory) research/science; immune regulation; kidney failure/injury; kidney transplantation/nephrology; pathology/histopathology; regenerative medicine; stem cells; tolerance; translational research/science