title: Immunosuppression with FTY720 and cyclosporine A inhibits rejection of adult porcine islet xenografts in rats.
abstract: BACKGROUND
  Our aim was to evaluate the effect of FTY720 in discordant islet xenotransplantation.
  
  
  METHODS
  Fetal porcine islet-like cell clusters (ICCs) were transplanted into normoglycemic rats that were either left untreated or treated with FTY720 only, with FTY720 plus cyclosporine A (CsA) or with CsA only. Twelve or 24 days after transplantation, graft morphology was evaluated immunohistochemically. Furthermore, adult porcine islets (APIs) were transplanted into diabetic rats immunosuppressed with FTY720 plus CsA. Blood glucose and porcine C-peptide levels were monitored.
  
  
  RESULTS
  In untreated rats, the ICC xenografts were completely rejected after 12 days. Treatment with CsA had only a marginal effect on the rejection. In animals given FTY720, only the number of infiltrating cells was somewhat reduced. However, at 12 days, no intact ICCs remained. Immunosuppression with FTY720 plus CsA had a marked inhibitory effect on islet xenograft rejection and plentiful morphologically intact ICCs remained. Twelve days after transplantation, only occasional macrophages and T cells could be detected. At 24 days after transplantation, the findings were similar. Furthermore, diabetic rats transplanted with APIs and immunosuppressed with FTY720 plus CsA remained normoglycemic for 53.0+/-15.8 days. In fact, one animal remained normoglycemic for more than 100 days. Serum levels of porcine C-peptide remained at levels similar to those for human C-peptide in healthy individuals.
  
  
  CONCLUSIONS
  Immunosuppression with FTY720 plus CsA inhibited almost all morphological signs of pig-to-rat islet xenograft rejection for up to 24 days after transplantation. Diabetic rats transplanted with APIs and immunosuppressed with FTY720 plus CsA remained normoglycemic for 53.0+/-15.8 days.
authors.affiliation: Department of Transplantation Surgery, Karolinska Institute, Huddinge University Hospital, Huddinge, Sweden.
authors.forename: A
authors.initials: A
authors.lastname: Maeda
authors.forename: M
authors.initials: M
authors.lastname: Goto
authors.forename: J
authors.initials: J
authors.lastname: Zhang
authors.forename: W
authors.initials: W
authors.lastname: Bennet
authors.forename: C G
authors.initials: CG
authors.lastname: Groth
authors.forename: O
authors.initials: O
authors.lastname: Korsgren
authors.forename: L
authors.initials: L
authors.lastname: Wennberg
mesh_terms: D000818:Animals; D001772:Blood Cell Count; D016572:Cyclosporine / Q000627:therapeutic use*; D003921:Diabetes Mellitus, Experimental / Q000601:surgery; D004359:Drug Therapy, Combination; D005260:Female; D000068876:Fingolimod Hydrochloride; D006084:Graft Rejection / Q000517:prevention & control*; D007165:Immunosuppression Therapy; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D016381:Islets of Langerhans Transplantation / Q000276:immunology; D007518:Isoantibodies / Q000032:analysis; D051379:Mice; D008819:Mice, Nude; D011409:Propylene Glycols / Q000627:therapeutic use*; D051381:Rats; D011917:Rats, Inbred Lew; D013110:Sphingosine / Q000031:analogs & derivatives; D013552:Swine; D014183:Transplantation, Heterologous / Q000276:immunology
chemical_list: D007166:Immunosuppressive Agents; D007518:Isoantibodies; D011409:Propylene Glycols; D016572:Cyclosporine; D000068876:Fingolimod Hydrochloride; D013110:Sphingosine