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vascular composite allograft

J Rodrigo Diaz-Siso, Zachary M Borab, Natalie M Plana, Brendan Parent, John T Stranix, Eduardo D Rodriguez
Technical success has been achieved in several forms of vascularized composite allotransplantation, including hand, face, penis, and lower extremity. However, the risks of lifelong immunosuppression have limited these procedures to a select group of patients for whom nontransplant alternatives have resulted in unsatisfactory outcomes. Recent reports of facial allograft failure, and subsequent reconstruction using autologous tissues, have reinforced the idea that a surgical contingency plan must be in place in case this devastating complication occurs...
November 2018: Plastic and Reconstructive Surgery
Hynek Mergental, Barnaby T F Stephenson, Richard W Laing, Amanda J Kirkham, Desley A H Neil, Lorraine L Wallace, Yuri L Boteon, Jeannette Widmer, Ricky H Bhogal, M Thamara P R Perera, Amanda Smith, Gary M Reynolds, Christina Yap, Stefan G Hübscher, Darius F Mirza, Simon C Afford
Increased use of high-risk allografts is critical to meet the demand for liver transplantation. We aimed to identify criteria predicting viability of organs, currently declined for clinical transplantation, using functional assessment during normothermic machine perfusion (NMP). Twelve discarded human livers were subjected to NMP following static cold storage. Livers were perfused with a packed red cell-based fluid at 37°C for 6 hours. Multilevel statistical models for repeated measures were employed to investigate the trend of perfusate blood gas profiles and vascular flow characteristics over time and the effect of lactate-clearing (LC) and non-lactate-clearing (non-LC) ability of the livers...
October 2018: Liver Transplantation
Nicco Krezdorn, Christine G Lian, Michael Wells, Luccie Wo, Sotirios Tasigiorgos, Shuyun Xu, Thiago J Borges, Rayven M Frierson, Ewelina Stanek, Leonardo V Riella, Bohdan Pomahac, George F Murphy
Face vascularized composite allografts (FVCAs) have helped patients with severe facial disfigurement, with acute rejection now largely controlled through iatrogenic immunosuppression. However, little is known regarding the incidence and mechanism(s) of more long-term pathologic alterations in FVCAs that may affect function and graft durability. Protocol surveillance biopsy specimens for up to an 8-year interval in 7 patients who received FVCAs at our institution revealed histopathologic evidence of chronic rejection...
October 12, 2018: American Journal of Transplantation
Shaun D Mendenhall, Michael T Ginnetti, Justin D Sawyer, Steven J Verhulst, Bradford L West, L Scott Levin, Michael W Neumeister
Background: Vascularized composite allotransplantation (VCA) is an emerging and growing field. Little is known about the prevalence and distribution of the adult potential donor population in the United States now that it falls under the oversight of the United Network for Organ Sharing (UNOS). Methods: We assessed the UNOS database from 2008 to 2015 to estimate the prevalence and distribution of adult potential vascularized composite allograft donors. Donor inclusion and exclusion criteria were developed in a way to minimize risk to recipients and were applied to the dataset...
June 2018: Plastic and Reconstructive Surgery. Global Open
Jessica B Chang, William J Rifkin, Marc A Soares, April Duckworth, Nakul Rao, Yee Cheng Low, Jonathan P Massie, Piul S Rabbani, Pierre B Saadeh, Daniel J Ceradini
Background: Widespread application of vascularized composite allotransplantation (VCA) is currently limited by the required lifelong systemic immunosuppression and its associated morbidity and mortality. This study evaluated the efficacy of ex vivo (after procurement but before transplantation) engineering of allografts using small interfering RNA to knockdown major histocompatibility complex I (MHC-I) and prolong rejection-free survival. Methods: Endothelial cells (ECs) were transfected with small interfering RNA targeted against MHC-I (siMHC-I) for all in vitro experiments...
June 2018: Plastic and Reconstructive Surgery. Global Open
Jennifer L Wainright, Christopher L Wholley, John Rosendale, Wida S Cherikh, Darren Di Battista, David K Klassen
BACKGROUND: Vascularized composite allograft (VCA) transplants include diverse organ types and are made possible primarily by deceased donors. METHODS: We used Organ Procurement and Transplantation Network (OPTN) data to characterize VCA deceased donors (n=66 of 70) in the United States 1998-2017 and compare their characteristics with those of kidney donors in 2017. RESULTS: Through December 31, 2017, 20 transplant programs performed 72 deceased donor VCA transplants, with organs donated by 70 donors, including 30 upper limb (17 unilateral and 13 bilateral) and 11 face donors...
September 17, 2018: Transplantation
Rushi V Parikh, Kiran Khush, Helen Luikart, Charlotte Sakarovitch, Justin Lee, Manisha Desai, Hannah Valantine, Alan C Yeung, William F Fearon
Asymmetric dimethylarginine (ADMA) is a key mediator of vascular homeostasis and an independent predictor of the development of accelerated cardiac allograft vasculopathy after heart transplantation. However, its association with clinical outcomes in heart transplant recipients has not been described. Plasma levels of ADMA were assayed within 8weeks following transplantation (baseline) using a competitive enzyme-linked immunosorbent assay. The primary end point was the composite of nonfatal myocardial infarction, percutaneous coronary intervention, retransplantation, or death at 5-year follow-up...
August 21, 2018: American Journal of Cardiology
Anette Weyergang, Ane S Fremstedal, Ellen Skarpen, Qian Peng, Khalid A Mohamedali, Marius S Eng, Lawrence H Cheung, Michael G Rosenblum, Johannes Waltenberger, Kristian Berg
Interactions between stromal cells and tumor cells pay a major role in cancer growth and progression. This is reflected in the composition of anticancer drugs which includes compounds directed towards the immune system and tumor-vasculature in addition to drugs aimed at the cancer cells themselves. Drug-based treatment regimens are currently designed to include compounds targeting the tumor stroma in addition to the cancer cells. Treatment limiting adverse effects remains, however, one of the major challenges for drug-based therapy and novel tolerable treatment modalities with diverse high efficacy on both tumor cells and stroma is therefore of high interest...
October 28, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
April Adams Szafran, Richard Redett, Arthur L Burnett
Penile transplantation using vascularized composite allografts is an emerging technique to treat genital loss. In the United States, this procedure has been performed successfully at Massachusetts General Hospital in a patient who had previously undergone treatment for penile cancer. The Johns Hopkins Medical Institutions has developed a research protocol to perform penile transplantation in patients with genital loss secondary to trauma. The process of selecting the appropriate candidate for genitourinary (GU) vascularized composite allograft surgery is rigorous including extensive physical examination, laboratory testing, imaging and psychological evaluations...
August 2018: Translational Andrology and Urology
Hui-Yun Cheng, Sheri K L Tay, Chih-Jen Wen, Chih-Fan Lin, Aline Yen-Ling Wang, Ling-Yi Shih, Shiao-Chin Liu, Eiji Kobayashi, Cheng-Hung Lin, Fu-Chan Wei
BACKGROUND: Tipping the balance toward regulatory T cells (Tregs) through adoptive cell therapy has shown promise to induce transplantation tolerance. Although such strategy has been explored in many mice organ transplantation studies, less knowledge was available in rat systems. Furthermore, the behaviors of the transferred cells have not been well studied in real-time fashion. METHODS: Tregs from naïve LEW rats were purified in two steps with the autoMACS system...
2018: PloS One
Thomas H Tung, Susan E Mackinnon
PURPOSE OF REVIEW: The current review will discuss the current understanding of nerve regeneration in vascularized composite allotransplantation (VCA). The success of proximal arm and leg transplants has been hampered by the limitations of nerve regrowth across long distances resulting in poor regeneration and functional recovery. Relevant research in stem-cell therapies to overcome these issues will be reviewed. RECENT FINDINGS: The effect of rejection on nerve regeneration in the VCA may be unpredictable and may be quite different for the nerve allograft...
October 2018: Current Opinion in Organ Transplantation
Emmanuel Morelon, Palmina Petruzzo, Jean Kanitakis
PURPOSE OF REVIEW: Vascularized composite allografts (VCA), which restore severely damaged body parts that cannot be repaired with conventional surgical techniques, often undergo acute skin rejection episodes in the early postgraft period. Although the risk of human VCA to be affected by chronic rejection was initially unknown, such cases were recently observed. RECENT FINDINGS: Chronic rejection targets preferentially the skin (dermal sclerosis, adnexal atrophy, necrosis) and vessels (graft vasculopathy) and may cause graft dysfunction, often resulting in ischemic graft loss...
October 2018: Current Opinion in Organ Transplantation
Charles Anton Fries, Carole Yasay Villamaria, Jerry Richard Spencer, Shari Lawson, Lin Wang, Thomas Raj, E George Wolf, Bijaya Kumar Parida, Vijay Saradhi Gorantla, Rory Frederick Rickard, Michael Robert Davis
BACKGROUND:  Ischemia-reperfusion injury (IRI) precipitates acute rejection of vascularized composite allografts (VCA). Hyperbaric preservation of tissues ex vivo, between harvest and revascularization, may reduce IRI and mitigate acute rejection of VCA. METHODS:  A porcine heterotopic musculocutaneous gracilis flap model was used. In phase 1, control autografts ( n  = 5) were infused with University of Wisconsin Solution (UWS) and stored at 4°C for 3 hours...
August 12, 2018: Journal of Reconstructive Microsurgery
Wida S Cherikh, Linda C Cendales, Christopher L Wholley, Jennifer Wainright, Vijay S Gorantla, David K Klassen, Sue V McDiarmid, Lawrence Scott Levin
On July 3, 2014, the Organ Procurement and Transplantation Network/United Network for Organ Sharing was charged with the oversight of vascularized composite allograft (VCA) procurement and transplantation in the United States. As of December 31, 2017, 61 VCA programs at 27 centers were approved in the United States. Fifty candidates have been added to the waiting list at 15 centers. Twenty-eight VCA transplants have been performed at 14 programs (10 upper limb, 10 uterus, 5 craniofacial, 1 scalp, 1 abdominal wall, and 1 penile)...
August 9, 2018: American Journal of Transplantation
Laura C Burlage, Shannon N Tessier, Joanna W Etra, Korkut Uygun, Gerald Brandacher
PURPOSE OF REVIEW: In this review, we discuss novel strategies that allow for extended preservation of vascularized composite allografts and their potential future clinical implications for the field of vascularized composite allotransplantation (VCA). RECENT FINDINGS: The current gold standard in tissue preservation - static cold preservation on ice - is insufficient to preserve VCA grafts for more than a few hours. Advancements in the field of VCA regarding matching and allocation, desensitization, and potential tolerance induction are all within reasonable reach to achieve; these are, however, constrained by limited preservation time of VCA grafts...
October 2018: Current Opinion in Organ Transplantation
SangMin Kim, Yong-Seok Han, Jun Hee Lee, Sang Hun Lee
Mesenchymal stem cells (MSCs) are widely used in transplantation therapy due to their multilineage differentiation potential, abundance, and immuno-modulating ability. However, the risk of allograft rejection limits their application. Here, we proposed a novel method to facilitate MSC transplantation with enhanced applicability and efficacy. We cultured human adipose-derived MSCs in a 3D culture under in vitro expansion conditions and under conventional 2D adherent culture conditions. MSC spheroids promoted extracellular matrix molecules that stimulate MSC proliferation, and produced more angiogenic cytokines such as vascular endothelial growth factor, hepatocyte growth factor, and fibroblast growth factor than 2D-cultured MSCs...
August 2018: Tissue & Cell
Nicco Krezdorn, Sotirios Tasigiorgos, Luccie Wo, Rachel Lopdrup, Marvee Turk, Harriet Kiwanuka, Salman Ahmed, Palmina Petruzzo, Ericka Bueno, Bohdan Pomahac, Leonardo V Riella
Background: Kidney dysfunction is a major complication after nonrenal solid organ transplants. Transplantation of vascularized composite allografts (VCA) has yielded successful midterm outcomes despite high rates of acute rejection and greater requirements of immunosuppression. Whether this translates in higher risks of kidney complications is unknown. Methods: Ninety-nine recipients of facial or extremity transplants from the Brigham and Women's Hospital (BWH) and the International Registry on Hand and Composite Tissue Transplantation (IR) were reviewed...
July 2018: Transplantation Direct
Bohdan Pomahac, Muayyad Alhefzi, Ericka M Bueno, Sue V McDiarmid, L Scott Levin
Living donation has become a medically and ethically accepted practice in solid organ transplantation. Published proceedings from the international kidney transplant community and from the Ethics Committee of The Transplantation Society articulated the general principles and specific recommendations for living donation, which remain the backbone of Centers for Medicare and Medicaid Services and Organ Procurement and Transplantation Network requirements and policies. Meanwhile, there have been major advancements in another revolutionary field of transplant medicine: vascularized composite allotransplantation...
September 2018: Plastic and Reconstructive Surgery
Bruce E Gelb, J Rodrigo Diaz-Siso, Natalie M Plana, Adam Jacoby, William J Rifkin, Kimberly S Khouri, Daniel J Ceradini, Eduardo D Rodriguez
Background: Donor-specific antibodies (DSA) to human leukocyte antigen increase the risk of accelerated rejection and allograft damage and reduce the likelihood of successful transplantation. Patients with full-thickness facial burns may benefit from facial allotransplantation. However, they are at a high risk of developing DSA due to standard features of their acute care. Case Presentation: A 41-year-old male with severe disfigurement from facial burns consented to facial allotransplantation in 2014; panel reactive antibody score was 0%...
2018: Case Reports in Transplantation
Jennifer L Wainright, Christopher L Wholley, Wida S Cherikh, Jennifer M Musick, David K Klassen
BACKGROUND: Vascularized Composite Allograft (VCA) transplantation is a developing area in the field of transplantation. METHODS: This study used Organ Procurement and Transplantation Network (OPTN) VCA waiting list and transplant data from July 3, 2014 through February 28, 2018 to characterize the OPTN VCA waiting list in terms of composition, removal patterns, waiting time, resulting transplants, and trends over time. RESULTS: Between implementation of the OPTN VCA waiting list on July 3, 2014 and February 28, 2018, 54 candidates - 53...
April 30, 2018: Transplantation
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