Preclinical Studies in Vascularized Composite Allotransplantation

Abstract

Introduction: Since 1998, when the first hand transplant was performed, Vascularized Composite Allotransplantation (VCA) field represents a new dimension in reconstructive surgery, offering a viable treatment option for injuries and defects that involve multiple layers of functional tissue, impossible to repair using conventional surgical techniques. Worldwide experience includes allotransplantation of upper and lower extremities, face, trachea, larynx, abdominal wall, uterus and penis, with promising clinical results. The major challenge remains at the immunologic level, translational ongoing studies being focused to develop less toxic immunosuppressant drugs and possibly achieve donor-specific tolerance. Materials and Methods: We conducted a series of preclinical studies of vascularized composite allotransplantation in preparation for further translation to clinical applications of this field. Our experience includes experimental vascularized allotransplantation models in rats exploring technical particularities and also analyzing the role of microchimerism in immunomodulation and promoting of the immune tolerance. Also, we performed a cadaveric study in order to explore the surgical techniques required in abdominal wall allotransplantation and the use of iliac crest as a potential microsurgical model of vascularized bone marrow transplantation(VBMT). Results: Working on small animal models allows the familiarization with microsurgical techniques in experimental composite tissue allotransplantation and evaluation of important immunological aspects: rejection dynamics, immunosuppression protocol testing and induction of immunologic tolerance. The surgical procedures performed in cadaveric models shown the feasibility of the abdominal wall allotransplantation procedure which may be translated to future clinical practice in association with organ transplantation. It may be possible to develop an alternative approach for iliac crest microsurgical transplant as tolerogenic strategy in solid organs or vascularized composite allotransplantation. Conclusion: Preclinical experience represents a mandatory step in developing a vascularized composite allotransplantation program, translating the knowledge obtained from experimental animal research and cadaveric studies to further clinical practice, ensuring optimal results for patients with complex tissue defects.