title: Tacrolimus inhibits the revascularization of isolated pancreatic islets.
abstract: OBJECTIVE
  Immunosuppressive drugs could be crucial factors for a poor outcome after islet allotransplantation. Unlike rapamycin, the effects of tacrolimus, the current standard immunosuppressant used in islet transplantation, on graft revascularization remain unclear. We examined the effects of tacrolimus on islet revascularization using a highly sensitive imaging system, and analyzed the gene expression in transplanted islets by introducing laser microdissection techniques.
  
  
  METHODS
  Islets isolated from C57BL/6-Tg (CAG-EGFP) mice were transplanted into the nonmetallic dorsal skinfold chamber on the recipients. Balb/c athymic mice were used as recipients and were divided into two groups: including a control group (n = 9) and tacrolimus-treated group (n = 7). The changes in the newly-formed vessels surrounding the islet grafts were imaged and semi-quantified using multi-photon laser-scanning microscopy and a Volocity system. Gene expression in transplanted islets was analyzed by the BioMark dynamic system.
  
  
  RESULTS
  The revascularization process was completed within 14 days after pancreatic islet transplantation at subcutaneous sites. The newly-formed vascular volume surrounding the transplanted islets in the tacrolimus-treated group was significantly less than that in the control group (p<0.05). Although the expression of Vegfa (p<0.05) and Ccnd1 (p<0.05) was significantly upregulated in the tacrolimus-treated group compared with that of the control group, no differences were observed between the groups in terms of other types of gene expression.
  
  
  CONCLUSIONS
  The present study demonstrates that tacrolimus inhibits the revascularization of isolated pancreatic islets without affecting the characteristics of the transplanted grafts. Further refinements of this immunosuppressive regimen, especially regarding the revascularization of islet grafts, could improve the outcome of islet allotransplantation.
authors.affiliation: Division of Advanced Surgical Science and Technology, Tohoku University, Sendai, Japan.
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Nishimura
authors.forename: Sho
authors.initials: S
authors.lastname: Nishioka
authors.forename: Ikuma
authors.initials: I
authors.lastname: Fujisawa
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Shiku
authors.forename: Miki
authors.initials: M
authors.lastname: Shimada
authors.forename: Satoshi
authors.initials: S
authors.lastname: Sekiguchi
authors.forename: Keisei
authors.initials: K
authors.lastname: Fujimori
authors.forename: Akira
authors.initials: A
authors.lastname: Ushiyama
authors.forename: Tomokazu
authors.initials: T
authors.lastname: Matsue
authors.forename: Noriaki
authors.initials: N
authors.lastname: Ohuchi
authors.forename: Susumu
authors.initials: S
authors.lastname: Satomi
authors.forename: Masafumi
authors.initials: M
authors.lastname: Goto
mesh_terms: D000818:Animals; D005786:Gene Expression Regulation / Q000187:drug effects; D021621:Imaging, Three-Dimensional; D007515:Islets of Langerhans / Q000098:blood supply* / Q000187:drug effects / Q000378:metabolism; D016381:Islets of Langerhans Transplantation; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D012885:Skinfold Thickness; D016559:Tacrolimus / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D013997:Time Factors
chemical_list: D016559:Tacrolimus