title: Mitomycin-C-treated peripheral blood mononuclear cells (PBMCs) prolong allograft survival in composite tissue allotransplantation.
abstract: BACKGROUND
  Composite tissue allotransplantation (CTA) was introduced as a potential treatment for complex reconstructive procedures and has become a clinical reality. Hand and face transplantation, the most widely recognized forms of CTA, have intensified immunological research in this emerging field of transplantation. Mitomycin C (MMC) is an alkylating agent that suppresses allogeneic T-cell responses. MMC-treated dendritic cells/PBMCs have been shown to induce donor-specific tolerance in solid organ allograft transplantations.
  
  
  METHODS
  Fully mismatched rats were used as hind limb donors [Lewis (RT1(1))] and recipients [Brown-Norway (RT1(n))]. Fifty-five allogeneic hind limb transplantations were accomplished in six groups. Group A (n = 10) received donor-derived MMC-treated PBMCs on transplantation day. Group B (n = 10) rats received no immunosuppression, group C (n = 10) received FK506 and prednisolon, group D consisted in isograft transplantation without immunosuppression, group E (n = 10) received non-treated PBMCs, and group F (n = 5) received PBS without any donor-derived cells. Rejection was assessed clinically and histologically.
  
  
  RESULTS
  In group A, the survival times of the allografts were prolonged to an average of 8.0 d. Rejection was significantly delayed compared with the averages of the corresponding control groups B, E, and F (5.5, 5.9, and 5.8 d). No rejection was seen in control groups C and D.
  
  
  CONCLUSIONS
  These results demonstrate that MMC-treated donor PBMCs significantly prolong allograft survival when administered systemically on the day of transplantation. However, the immunomodulatory effect is relatively modest with further research being required to clarify dose-effect relations, cell characteristics, and an optimized mechanism and timing for cell application.
authors.affiliation: Department of Hand, Plastic, and Reconstructive Surgery, Burn Center, BG Trauma Center Ludwigshafen, Plastic and Hand Surgery, University of Heidelberg, Germany. Christian.Radu@uni-heidelberg.de
authors.forename: Christian Andreas
authors.initials: CA
authors.lastname: Radu
authors.forename: Jurij
authors.initials: J
authors.lastname: Kiefer
authors.forename: Dominik
authors.initials: D
authors.lastname: Horn
authors.forename: Christian
authors.initials: C
authors.lastname: Kleist
authors.forename: Laura
authors.initials: L
authors.lastname: Dittmar
authors.forename: Flavius
authors.initials: F
authors.lastname: Sandra
authors.forename: Martin
authors.initials: M
authors.lastname: Rebel
authors.forename: Henning
authors.initials: H
authors.lastname: Ryssel
authors.forename: Eva
authors.initials: E
authors.lastname: Koellensperger
authors.forename: Martha M
authors.initials: MM
authors.lastname: Gebhard
authors.forename: Marcus
authors.initials: M
authors.lastname: Lehnhardt
authors.forename: Guenter
authors.initials: G
authors.lastname: Germann
authors.forename: Peter
authors.initials: P
authors.lastname: Terness
mesh_terms: D019264:Adoptive Transfer; D000477:Alkylating Agents / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000276:immunology; D001706:Biopsy; D006084:Graft Rejection / Q000276:immunology / Q000473:pathology / Q000517:prevention & control; D006614:Hindlimb / Q000276:immunology / Q000637:transplantation*; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000276:immunology / Q000637:transplantation*; D008297:Male; D016685:Mitomycin / Q000494:pharmacology*; D051381:Rats; D011914:Rats, Inbred BN; D011917:Rats, Inbred Lew; D014181:Transplantation Immunology / Q000187:drug effects* / Q000276:immunology; D023001:Transplantation Tolerance / Q000187:drug effects / Q000276:immunology; D014184:Transplantation, Homologous
chemical_list: D000477:Alkylating Agents; D016685:Mitomycin