title: Mouse hind limb transplantation: a new composite tissue allotransplantation model using nonsuture supermicrosurgery.
abstract: BACKGROUND
  The development of microsurgical techniques has facilitated the establishment of vascularized composite tissue transplant models in small mammals. Because the mouse would be the ideal model to study various composite tissue allotransplantation (CTA)-related problems, we designed two new surgical techniques for orthotopic (ORT) and heterotopic (HET) hind limb transplantation.
  
  
  METHODS
  BALB/c hind limbs were transplanted to BALB/c or C57BL6 recipients using a nonsuture cuff technique. ORT: donor femoral vessels were anastomosed to recipient femoral vessels, the sciatic nerve approximated end-to-end and osteosynthesis was performed using an intramedullary rod. HET/cervical: Donor femoral vessels of a reduced size osteomyocutaneous hind limb CTA were anastomosed to recipient common carotid artery and external jugular vein without nerve approximation.
  
  
  RESULTS
  Both procedures could be performed with a high success rate (ORT: 62%; HET: 90%). Donor operation lasted for 100±12 min and recipient operation 114±27 min (ORT) and 54±16 min (HET). Complication rates in terms of bleeding, and thrombosis at the cuff side was slightly higher in the ORT group. All syngeneic grafts survived long term (>100 days). FK506 (2 mg/kg) significantly prolonged graft survival (87±22 days) when compared with untreated controls (6±1 day). Functional evaluation of ORT grafts by means of video gait kinematics and CatWalk analysis revealed specific differences of gait parameters when compared with nontransplanted controls (P<0.05).
  
  
  CONCLUSIONS
  The ORT hind limb transplant model seems to be best suited to study functional outcome and nerve regeneration in CTA. The technically less demanding HET/cervical model may be used to investigate basic immunology and clinically relevant questions related to acute and chronic rejection, and ischemia reperfusion injury in reconstructive transplantation.
authors.affiliation: Division of Plastic and Reconstructive Surgery, University of Pittsburgh, Pittsburgh, PA, USA. robert.sucher@i-med.ac.at
authors.forename: Robert
authors.initials: R
authors.lastname: Sucher
authors.forename: Cheng-Hung
authors.initials: CH
authors.lastname: Lin
authors.forename: Rami
authors.initials: R
authors.lastname: Zanoun
authors.forename: Komli-Kofi
authors.initials: KK
authors.lastname: Atsina
authors.forename: Matthias
authors.initials: M
authors.lastname: Weinstock
authors.forename: Benson
authors.initials: B
authors.lastname: Pulikkotil
authors.forename: Stefan
authors.initials: S
authors.lastname: Schneeberger
authors.forename: Xin Xiao
authors.initials: XX
authors.lastname: Zheng
authors.forename: Johann
authors.initials: J
authors.lastname: Pratschke
authors.forename: W P Andrew
authors.initials: WP
authors.lastname: Lee
authors.forename: Gerald
authors.initials: G
authors.lastname: Brandacher
mesh_terms: D000671:Amputation, Surgical; D000818:Animals; D005684:Gait; D006084:Graft Rejection / Q000473:pathology; D006614:Hindlimb / Q000033:anatomy & histology / Q000473:pathology / Q000637:transplantation*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008866:Microsurgery / Q000379:methods*; D023421:Models, Animal; D009416:Nerve Regeneration; D009929:Organ Size; D016042:Transplantation, Heterotopic / Q000379:methods; D014184:Transplantation, Homologous / Q000379:methods / Q000473:pathology; D014185:Transplantation, Isogeneic