Vascularized Composite Allotransplantation Research: The Emerging Field

Abstract

To the Editor: This letter states the position of the Vascularized Composite Allotransplantation (VCA) Committee of the American Society of Transplantation regarding VCA research. Success with solid organs has led to the application of transplantation technology for unreconstructable VC tissue injuries. VCA composed of muscle, bone, nerve, skin and others are transplanted as single functional units (e.g. hands, faces) from a deceased donor to a patient. VCA replaces tissues lost in traumatic incidents or through other causes. Like solid organs, VCA have limited acceptable ischemia time and require donor–recipient matching. For severe defects that cannot be reconstructed with autologous tissue, VCA can achieve near-normal restoration and improved functional outcomes. More than 90 patients worldwide have received VCA, with promising functional outcomes and allograft survival. VCA is evolving into an important approach to complex reconstructions. Given its risks, expense and complexity, VCA will likely be appropriate only for injuries imposing major functional or psychological deficits (1, 2). Investment to mature VCA research is essential. Animal models, translational research and clinical studies are needed to advance the understanding of VCA and optimize its outcomes. The unique mechanisms of VCA rejection must be elucidated. Unlike solid organs, VCA are composed of multiple tissues with different immunogenic properties; nonetheless, most VCA recipients receive immunosuppression regimens similar to those used in solid organ recipients (3, 4). Life-long immunosuppression appears necessary to prevent VCA rejection. This requirement may result in health complications accepted in life-saving solid organ transplantation, but VCA transplantation is not life-saving. For VCA implementation and clinical use, less toxic approaches must be developed. This requires investment in preclinical animal models and clinical trials. VCA has yet to develop accepted standards to define success. This limits the ability to interpret and compare outcomes from disparate groups, particularly in light of the small number of patients treated. Investment is necessary to validate the criteria for assessing complications, diagnosing immune rejection and comparing the results of VCA with other therapeutic options. Strategies for coping with therapy failure need to be developed and codified. VCA requires a highly multidisciplinary team, along with a comprehensive institutional infrastructure. Therefore, investments should be made in centers with clear institutional commitment to VCA, clinical transplantation, reconstructive surgery and trauma rehabilitation. Unlike organ transplants, the functionality of VCA depends on the growth of recipient nerves into the grafted donor tissue. Although nerve growth occurs, its rate is a limiting factor in the return of graft function. Understanding the mechanisms of nerve repair and growth will be required to optimize VCA. In summary, we recommend funding for research in VCA, prioritizing: Multicenter clinical outcome studies based on registry data to define: Optimal immunosuppression. Diagnostic criteria of rejection. Standards for measuring functional outcomes. Quality of life and socioeconomic outcomes. Basic research: To develop animal models to investigate unique immunological aspects of VCA. To explore VCA-specific aspects of rejection and treatment. The authors of this manuscript have no conflicts of interest to disclose as described by the American Journal of Transplantation.