title: Non-myeloablative conditioning is sufficient to induce mixed chimerism and subsequent acceptance of donor specific cardiac and skin grafts.
abstract: Organ transplant recipients have elevated cancer and viral infection risks due to immunosuppression and long-term results of organ transplantation remain unsatisfactory, mainly because of chronic rejection. The purpose of the current study is to establish a nonmyeloablative perioperative regimen, able to induce mixed chimerism and tolerance of allografts. To establish a nonmyeloablative perioperative regimen, we used Busulfan, an important component of many bone marrow transplantation preparative regimens for a variety of non-neoplastic diseases as an alternative to total body irradiation (TBI), and FTY720, a unique immunosuppression agent, inhibition lymphocyte homing. We found that creating a lymphohematopoietic chimera in which donor and recipient hematopoiesis coexist resulted in prolongation of the donor specific heart and skin allografts. Consistent with graft survival, pathological analysis indicated that the allografts from tolerant recipients were free of myocardial injury and had only a few interstitial infiltrates, and obliterative vasculopathy was not observed. Furthermore, we found that Treg cells were increased in the long-term graft acceptance recipients. Our data revealed that the therapeutic potential for using hematopoietic chimerism in non-myeloablated recipients hope the advances in rodent models described above in the development of minimal, nontoxic host conditioning regimens for mixed chimerism induction and subsequent acceptance of donor specific grafts.
authors: National Research Institute for Child Health and Development, Tokyo, Japan.
authors: Chi
authors: C
authors: Liu
authors: Ping
authors: P
authors: Zhu
authors: Taro
authors: T
authors: Saito
authors: Yoshitaka
authors: Y
authors: Isaka
authors: Yukitoshi
authors: Y
authors: Nagahara
authors: Jian
authors: J
authors: Zhuang
authors: Xiao-Kang
authors: XK
authors: Li
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D016026:Bone Marrow Transplantation; D002066:Busulfan / Q000008:administration & dosage; D002452:Cell Count; D000068876:Fingolimod Hydrochloride; D006085:Graft Survival; D049452:Green Fluorescent Proteins / Q000235:genetics; D015796:HLA-B27 Antigen / Q000235:genetics; D016027:Heart Transplantation; D007166:Immunosuppressive Agents / Q000008:administration & dosage; D007962:Leukocytes / Q000166:cytology; D019653:Myeloablative Agonists / Q000008:administration & dosage; D011409:Propylene Glycols / Q000008:administration & dosage; D051381:Rats; D011916:Rats, Inbred F344; D055647:Rats, Transgenic; D016038:Skin Transplantation; D013110:Sphingosine / Q000008:administration & dosage / Q000031:analogs & derivatives; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D018183:Transplantation Chimera; D019172:Transplantation Conditioning
chemical_list: D015796:HLA-B27 Antigen; D007166:Immunosuppressive Agents; D019653:Myeloablative Agonists; D011409:Propylene Glycols; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D002066:Busulfan; D000068876:Fingolimod Hydrochloride; D013110:Sphingosine