VCA in Rodents

Bahar Bassiri, Cleveland Clinic Foundation, Cleveland, OH, USA.

In the last decade, Vascularized Composite Allotransplantation has opened a new era in reconstructive surgery with a great potential for optimal functional and aesthetic restoration of complex disabling and disfiguring defects secondary to trauma and cancer ablative surgeries.

In most applications, Vascularized Composite Allografts (VCA) contain multiple tissue components with unique immunologic characteristics such as skin, fat, muscle, nerves, lymph nodes, bone, cartilage, ligaments, and bone marrow. Thus, VCAs are considered to be inherently more immunogenic than solid organ transplants and life-long immunosuppression is necessary to prevent rejection and overcome the immunologic barrier.

To study the mechanisms of VCA acceptance and rejection, different experimental models, strategies, and different immunosuppressive protocols have been used. Rat is one of the most popular models for experimental research in transplantation because of an immune system similar to human (RT1complex: MHC Class I, II, III) and availability of inbred, mutant and recombinant strains with genetic characterization.

Here we summarize the current knowledge of immunologic aspects and tolerance-inducing strategies in rat models of VCA. These models include the following categories: VCAs containing only soft tissues (skin, adipose tissue, muscle, nerves and lymph nodes) such as groin flap, abdominal wall and face and VCAs containing vascularized bone marrow such as single and double femoral bone, iliac crest and limb allograft, face with bony components (mandible, maxilla, calvarium). This overview emphasizes the relevance and applicability of different VCAs to clinical cases of vascularized composite allotranplantation.

Learning objectives:

1. To become familiar with the different types of VCA available in rat and their applicability to different clinical scenarios.
2. To understand the differences in immune response pertinent to different types of VCAs and to become familiar the role of chimerism and strategies for tolerance induction
3. To recognize advantages and disadvantages of application of a rat model in VCA.