title: Assessing the effect of immunosuppression on engraftment of pancreatic islets.
abstract: BACKGROUND
  In addition to ischemia and immunologic factors, immunosuppressive drugs have been suggested as a possible contributing factor to the loss of functional islets after allogeneic islet cell transplantation. Using our previously described islet-kidney (IK) transplantation model in miniature swine, we studied whether an islet-toxic triple-drug immunosuppressive regimen (cyclosporine+azathioprine+prednisone) affects the islet engraftment process and thus long-term islet function.
  
  
  METHODS
  Donor animals underwent partial pancreatectomy, autologous islet preparation, and injection of these islets under the autologous kidney capsule to prepare an IK. Experimental animals received daily triple-drug immunosuppression during the islet engraftment period. Control animals did not receive any immunosuppression during this period. Four to 8 weeks later, these engrafted IK were transplanted across a minor histocompatibility mismatched barrier into pancreatectomized, nephrectomized recipient animals at an islet dose of approximately 4500 islet equivalents/kg recipient weight. Cyclosporine was administered for 12 days to the recipients to induce tolerance of the IK grafts and the animals were followed long-term.
  
  
  RESULTS
  Diabetes was corrected by IK transplantation in all pancreatectomized recipients on both the control arm (n=3) and the experimental arm (n=4) of the study and all animals showed normal glucose regulation over the follow-up period. Intravenous glucose tolerance tests performed at 1, 2, and 3 or more months after IK transplantation showed essentially equivalent glycemic control in both control and experimental animals.
  
  
  CONCLUSIONS
  In this preclinical in vivo large animal model of islet transplantation, the effect of triple-drug immunosuppression on islet function does not negatively affect islet engraftment as assessed by the long-term function of engrafted islets.
authors.affiliation: Transplantation Biology Research Center, Massachusetts General Hospital, 13th Street, Boston, MA 02129, USA.
authors.forename: Prashanth
authors.initials: P
authors.lastname: Vallabhajosyula
authors.forename: Atsushi
authors.initials: A
authors.lastname: Hirakata
authors.forename: Akira
authors.initials: A
authors.lastname: Shimizu
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Okumi
authors.forename: Vaja
authors.initials: V
authors.lastname: Tchipashvili
authors.forename: Hanzhou
authors.initials: H
authors.lastname: Hong
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Yamada
authors.forename: David H
authors.initials: DH
authors.lastname: Sachs
mesh_terms: D000818:Animals; D001379:Azathioprine / Q000008:administration & dosage / Q000009:adverse effects; D001786:Blood Glucose / Q000378:metabolism; D016572:Cyclosporine / Q000008:administration & dosage / Q000009:adverse effects; D003922:Diabetes Mellitus, Type 1 / Q000503:physiopathology / Q000601:surgery; D004359:Drug Therapy, Combination; D007165:Immunosuppression Therapy / Q000009:adverse effects; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000009:adverse effects; D016381:Islets of Langerhans Transplantation / Q000009:adverse effects / Q000276:immunology* / Q000502:physiology; D023421:Models, Animal; D011241:Prednisone / Q000008:administration & dosage / Q000009:adverse effects; D013552:Swine; D013556:Swine, Miniature; D023001:Transplantation Tolerance / Q000187:drug effects; D014184:Transplantation, Homologous
chemical_list: D001786:Blood Glucose; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D001379:Azathioprine; D011241:Prednisone