The limited availability of autologous tissue for reconstructing large defects after tumor resection, burn and traumatic injury, or congenital deformities remains a challenging clinical problem. Indeed, severe anatomical defect is unsalvageable by conventional surgery. To overcome this issue, over the last 20 years scientific surgeons have worked on an innovative procedure allowing anatomical restoration ("like to like"): vascularized composite allograft (VCA).

While the exact numbers on the waiting list for any and all types of VCA remain unknown, as of 2005, there were approximately 976,000 limb amputees in the United States, and this number is predicted to grow exponentially over the coming years [1]. Although lower extremity amputations are considerably more frequent, upper extremity function is more complex, and therefore more challenging to replicate with prosthetics [2]. Even then, patients often have great difficulty developing normalcy in performing the simplest of tasks, a most devastating setback. Along with chronic and phantom pain, limb amputees also struggle with psychological disorders, decreased quality of life and elevated healthcare costs. With upper extremity transplantation, the majority of recipients have yielded considerable return of sensorimotor function and dramatic improvement in one’s quality of life [3]. In contrast, the phenomenal success of solid organ transplantation (SOT) has led to demand outstripping supply such that >123,000 patients are on the waiting list at any time.  

To date, more than 130 upper extremity and 44 face allografts have been transplanted with improvement in functional and psychosocial outcomes [4,5]. Such VCAs contain various combinations of skin, muscle and bone, and require chronic immunosuppression. Yet, the incidence of acute rejection targeted at the skin within the first-year approaches 90% and requires additional systemic and/or local immunotherapy to halt progression, reverse the episode and prevent allograft loss [6]. However, current systemic immunosuppressive regimens subject patients to an increased risk of developing infectious, metabolic, reno-vascular and neoplastic complications [7]. However, the need for chronic immunosuppression to prevent graft rejection may pose unnecessarily high risk to patients for treating non life-threatening deficiencies.

 

Thus, our laboratory, in collaboration with the Center for Transplantation Science, is investigating means for inducing tolerance to vascularized limb tissue allografts using different technologies such as chimerism approach, tissue engineering, and perfusion machine.

Reference 

[1] Ziegler-Graham K, MacKenzie EJ, Ephraim PL, et al. Estimating the prevalence of limb loss in the United States: 2005 to 2050. Arch Phys Med Rehabil2008; 89: 422–9.

[2] Melcer T, Walker GJ, Galarneau M, et al. Midterm health and personnel outcomes of recent combat amputees. Mil Med2010; 175: 147–54.

[3] Petruzzo P, Dubernard JM. World experience after more than a decade of clinical hand transplantation: update on the French program. Hand Clin2011; 27: 411–6, vii

[4] Shores JT, Brandacher G, and Lee WP. Hand and upper extremity transplantation: an update of outcomes in the worldwide experience. Plast Reconstr Surg.2015;135(2):351e-60e.

[5] Sosin M, and Rodriguez ED. The Face Transplantation Update: 2016. Plast Reconstr Surg.2016;137(6):1841-50.

[6] Kueckelhaus M, Fischer S, Seyda M, Bueno EM, Aycart MA, Alhefzi M, ElKhal A, Pomahac B, and Tullius SG. Vascularized composite allotransplantation: current standards and novel approaches to prevent acute rejection and chronic allograft deterioration. Transpl Int.2016;29(6):655-62.

[7] Petruzzo P, Lanzetta M, Dubernard JM, Landin L, Cavadas P, Margreiter R, Schneeberger S, Breidenbach W, Kaufman C, Jablecki J, et al. The International Registry on Hand and Composite Tissue Transplantation. Transplantation.2010;90(12):1590-4.

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