title: Steroid-free maintenance of islet allografts using mycophenolate mofetil and cyclosporine in the non-human primate.
abstract: BACKGROUND
  Islet transplantation continues to be a promising treatment for type 1 diabetes, however, numerous limitations still prevent its widespread use. Many immunosuppressive medications used for islet transplantation are known to be diabetogenic. The goal of this study is to evaluate the short-term follow-up (90 day) of a steroid-free maintenance immunosuppression protocol of mycophenolate mofetil (MMF) and cyclosporine (CSA) in non-human primate islet allotransplantation.
  
  
  METHODS
  Diabetes was induced in the primate Macaca fascicularis via total pancreatectomy. Freshly isolated islets were autotransplanted (n=5) or allotransplanted (n=5) into the portal vein. Immunosuppression consisted of induction with rabbit anti-thymocyte globulin (ATG) and prednisone. CSA (25 mg/daily) and MMF (250 mg daily) were used for maintenance and given orally once daily throughout the 90 day study period. Fasting blood glucose measurements were used to monitor graft function. Intravenous glucose tolerance tests (IVGTT) were performed prior to pancreatectomy and at the study endpoint.
  
  
  RESULTS
  Average fasting blood glucose levels were elevated in diabetic controls (313.6 mg/dl ±51.8) and untreated allograft recipients (257 mg/dl ±61.0) post-transplant. Auto-transplanted animals and allograft recipients treated with immunosuppression, on the other hand, maintained normoglycemia (74.5 mg/dl ±20.9, 62.3 mg/dl ±4.40) throughout the follow-up period. Additionally, beta cell function and first phase insulin secretion did not differ significantly between auto-graft and immunosuppressed allo-graft recipients post-transplant.
  
  
  CONCLUSIONS
  We conclude that this steroid-free maintenance immunosuppression regimen is effective in maintaining islet allograft survival in the non-human primate and offers comparable graft function to that of autografts for up to 3 months post-transplant.
authors.affiliation: Department of Surgery, Division of Transplantation, The Ohio State University, Columbus, USA.
authors.forename: Jill
authors.initials: J
authors.lastname: Buss
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Essig
authors.forename: Kwame
authors.initials: K
authors.lastname: Osei
authors.forename: Sergey
authors.initials: S
authors.lastname: Brodsky
authors.forename: Gregg
authors.initials: G
authors.lastname: Hadley
authors.forename: Amer
authors.initials: A
authors.lastname: Rajab
mesh_terms: D000818:Animals; D016572:Cyclosporine / Q000494:pharmacology / Q000627:therapeutic use*; D003921:Diabetes Mellitus, Experimental / Q000628:therapy; D006085:Graft Survival / Q000187:drug effects*; D007165:Immunosuppression Therapy / Q000379:methods; D007166:Immunosuppressive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D016381:Islets of Langerhans Transplantation / Q000379:methods*; D008252:Macaca fascicularis; D009173:Mycophenolic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D007166:Immunosuppressive Agents; D016572:Cyclosporine; D009173:Mycophenolic Acid