The Neck as a Preferred Recipient Site for Vascularized Composite Allotransplantation in the Mouse

Abstract

This novel mouse model allows performing vascularized composite allotransplantation with very high success and survival rates. The advantages over conventional models are multifold. A high-flow common carotid artery keeps the anastomosis patent, and diastolic suction of the heart reduces the risk of venous stasis and thrombus formation. Less destruction because of the heterotopic positioning of the hindlimb graft further reduces the associated mortality and morbidity in this fragile model.

Preclinical Models in Vascularized Composite Allotransplantation

“…Other challenges in large animal research include splinting and immobilisation of limbs that can place very large demands on laboratory staff with respect to animal husbandry and may mandate longer durations of animal sedation, with concomitant risks to the experimental subject. As an example of this balance, Sucher et al report a significantly lower technical success rate in performing their orthotopic mouse hind limb transplant compared to their heterotopic model, a situation paralleled by our groups' experience in swine [23]. Zor 2010 [19] Hindlimb (OTH) Kim 1984 [20] Hindlimb (OTH)…”

“…Orthotopic models in small and large animals have been designed to address these questions. Technical success has been reported in orthotopic mouse hind limb transplantation [23,24] and motor and sensory nerve functions have been positively evaluated in orthotopic limb transplants in both rodents and NHPs [14,15,22]. Nonetheless, measuring functional recovery is a challenge and various strategies have been attempted.…”

Orthotopic Hind Limb Transplantation in the Mouse

“…Although there have been various small 13,16,18,20,25,26 and large animal 14,27-29 models described for VCA as recently reviewed by Brandacher et al 30 only very few are actually applicable for basic mechanistic immunological research 16,24,30 . Due to the small vessel diameter of the mouse femoral artery and vein, it requires advanced surgical and super-microsurgical training and skills to perform successful anastomosis as the key component of orthotopic hind limb transplantation.…”

“…Due to the small vessel diameter of the mouse femoral artery and vein, it requires advanced surgical and super-microsurgical training and skills to perform successful anastomosis as the key component of orthotopic hind limb transplantation. While meticulous and careful dissection of the anatomical structures is as critically relevant in this model as in previously published models 20,31,32 , the cuff technique has shown a less steep learning curve compared to suture anastomosis of sub-millimeter vessels 16,25 and can be achieved in a couple of months training with rigorous daily practice. Based on our experience, an untrained microsurgeon will need 30 -50 procedural attempts to acquire sufficient and reliable skills to perform this model with high success rates.…”

“…First and foremost, as reported previously by our group 16 , the cuff technique can be employed in vessels with a lumen diameter smaller than 1 millimeter, allowing for orthotopic transplantation of a hind limb allograft. This approach provides the basis for employing this model combined in both immunological as well as functional studies of nerve regeneration related to VCA 16,25 . Nerve regeneration is of key importance to the field of reconstructive transplantation, as these are non-life saving procedures whose success is primarily determined by the restoration of functional and aesthetic defects.…”