title: Local administration of Mitomycin-C-Treated peripheral blood mononuclear cells (PBMCs) prolongs allograft survival in vascularized composite allotransplantation.
abstract: BACKGROUND
  VCA offers a potential treatment for extensive tissue defects. First results of systemic administration of Mitomycin C-treated PBMCs in VCA demonstrated a significant prolongation of allograft survival. The aim of this study is to evaluate if local administration of MMC-PBMCs prolongs allograft survival in allogeneic hind limb transplantations of the rat.
  
  
  METHODS
  Sixty allogeneic hind limb transplantations in the rat were performed in six groups. Lewis rats (LEW) were used as hind limb donors and Brown-Norway rats (BN) as recipients. Animals in group A received donor-derived MMC-treated PBMCs locally (i.m.). Group B received no immunosuppressive therapy, group C received a standard immunosuppressive regime consisting of FK506 and Prednisolon, group D (BN to BN) comprised isograft transplantations without immunosuppressive treatment, group E received non-treated PBMCs (i.m.) and group F received phosphate buffered saline (PBS) without cells. The transplanted hind limbs were assessed for color, edema, skin, hair condition, and consistency of the thigh every 8 hours.
  
  
  RESULTS
  Rejection in group A was delayed to an average of 7.2 ± 0.6 days. Survival times were significantly prolonged (P < 0.01) compared to control groups B, E, and F (5.5 ± 0.7, 5.8 ± 0.7, and 5.7 ± 0.5 days). Control groups C and D showed no signs of rejection.
  
  
  CONCLUSIONS
  The findings of this study show that local administration of MMC-PBMCs has no side effects and significantly extends allograft survival. Further experiments with MMC-PBMCs treatments repeated at different time-points and being added to low dose immunosuppressive protocols need to be performed to improve experimental and eventually clinical outcome after VCA. © 2015 Wiley Periodicals, Inc. Microsurgery 36:417-425, 2016.
authors.affiliation: Department of Hand- Plastic- and Reconstructive Surgery, Burn Center, BG Trauma Center Ludwigshafen, Plastic- and Hand Surgery-University of Heidelberg, Heidelberg, Germany.
authors.forename: Christian Andreas
authors.initials: CA
authors.lastname: Radu
authors.affiliation: Department of Hand- Plastic- and Reconstructive Surgery, Burn Center, BG Trauma Center Ludwigshafen, Plastic- and Hand Surgery-University of Heidelberg, Heidelberg, Germany.
authors.forename: Jurij
authors.initials: J
authors.lastname: Kiefer
authors.affiliation: Department of Experimental Surgery, University of Heidelberg, Heidelberg, Germany.
authors.forename: Martha Maria
authors.initials: MM
authors.lastname: Gebhard
authors.affiliation: Department of Hand- Plastic- and Reconstructive Surgery, Burn Center, BG Trauma Center Ludwigshafen, Plastic- and Hand Surgery-University of Heidelberg, Heidelberg, Germany.
authors.forename: Amir Khosrow
authors.initials: AK
authors.lastname: Bigdeli
authors.affiliation: Department of Hand- Plastic- and Reconstructive Surgery, Burn Center, BG Trauma Center Ludwigshafen, Plastic- and Hand Surgery-University of Heidelberg, Heidelberg, Germany.
authors.forename: Volker Jürgen
authors.initials: VJ
authors.lastname: Schmidt
authors.affiliation: Department of Hand- Plastic- and Reconstructive Surgery, Clinic for Plastic and Reconstructive Surgery, Aesthetic and Preventive Medicine at Heidelberg University Hospital, Ethianum, Heidelberg, Germany.
authors.forename: Guenter
authors.initials: G
authors.lastname: Germann
authors.affiliation: Department of Plastic Surgery, Burn Center, Sarcoma Reference Center, BG-University Hospital Bergmannsheil, Bochum, Germany.
authors.forename: Marcus
authors.initials: M
authors.lastname: Lehnhardt
authors.affiliation: Department of Transplant Immunology, Institute for Immunology, University of Heidelberg, Heidelberg, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Terness
authors.affiliation: Department of Hand- Plastic- and Reconstructive Surgery, Burn Center, BG Trauma Center Ludwigshafen, Plastic- and Hand Surgery-University of Heidelberg, Heidelberg, Germany.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Kneser
authors.affiliation: Department of Hand- Plastic- and Reconstructive Surgery, Burn Center, BG Trauma Center Ludwigshafen, Plastic- and Hand Surgery-University of Heidelberg, Heidelberg, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Kremer