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vascular composite allograft

C Anton Fries, Shari D Lawson, Lin C Wang, Kai V Slaughter, Praveen K Vemula, Ashish Dhayani, Nitin Joshi, Jeffrey M Karp, Rory F Rickard, Vijay S Gorantla, Michael R Davis
BACKGROUND: Currently, patients receiving vascularized composite allotransplantation (VCA) grafts must take long-term systemic immunosuppressive therapy to prevent immunologic rejection. The morbidity and mortality associated with these medications is the single greatest barrier to more patients being able to receive these life-enhancing transplants. In contrast to solid organs, VCA, exemplified by hand or face transplants, allow visual diagnosis of clinical acute rejection (AR), directed biopsy and targeted graft therapies...
2019: PloS One
Marco Pappalardo, Luigi Montesano, Francesca Toia, Antonio Russo, Sara Di Lorenzo, Francesco Dieli, Francesco Moschella, Angelo A Leto Barone, Serena Meraviglia, Anna Barbara Di Stefano
Hand and face transplants are becoming increasingly common, recording progressively more penile, uterus, abdominal wall, and allotransplantation cases reported worldwide. Despite current protocols allow long-term survival of the allografts, the ultimate goal of donor-specific tolerance has not been achieved yet. In fact, the harmful adverse effects related to the lifelong administration of immunosuppressive agents are the main drawbacks for vascularized composite allotransplantations. Research is very active in investigating alternative methods to induce greater tolerance while minimizing toxicity...
February 2019: Annals of Plastic Surgery
C Anton Fries, Sharon D Lawson, Lin C Wang, Jerry R Spencer, Mark Roth, Rory F Rickard, Vijay S Gorantla, Michael R Davis
INTRODUCTION: Vascularized composite allotransplantation can reconstruct devastating tissue loss by replacing like-with-like tissues, most commonly in the form of hand or face transplantation. Unresolved technical and ethical challenges have meant that such transplants remain experimental treatments. The most significant barrier to expansion of this field is the requirement for systemic immunosuppression, its toxicity and effect on longevity.Hydrogen sulfide (H2S) has been shown experimentally to ameliorate the ischemia reperfusion injury associated with composite tissue autotransplantation, which has been linked to acute rejection in solid organ transplantation...
January 9, 2019: Annals of Plastic Surgery
Yaojun Wang, Yunfeng Xi, Fu Han, Yang Liu, Na Li, Zhongliang Ren, Jiajie Xue, Lei Guo, Dahai Hu
Mesenchymal stromal cells (MSCs) have been applied in prevention from allograft rejection based on their immunomodulatory effects. However, conflicting results have been presented among recent studies, for which one possibility being acknowledged is that the exact effect is determined by the microenvironment when MSCs are applied in vivo. Using a hind limb composite tissue allograft model, we investigate the influence of IFN-γ-preconditioning on the immunomodulatory effects of MSCs and the subsequent allograft survival...
January 7, 2019: Cell and Tissue Research
Hiroki Oda, Ryosuke Ikeguchi, Tomoki Aoyama, Souichi Ohta, Takashi Noguchi, Yukitoshi Kaizawa, Hirofumi Yurie, Hisataka Takeuchi, Sadaki Mitsuzawa, Koji Yamamoto, Shuichi Matsuda
BACKGROUND: Skin is considered to be the most antigenic component of all vascularized composite allotransplantation tissues. However, no studies have used methods other than histological assessment to analyze the relative antigenicity of various components. In this study, we analyzed gene expression to investigate the relative antigenicity of each component in the transplanted limb. METHODS: Seven Brown Norway rats and 31 Lewis rats were assigned to two groups: an allograft group and a syngeneic (control) group...
December 17, 2018: Microsurgery
Josef Stehlik, Brian Armstrong, David A Baran, Nancy D Bridges, Anil Chandraker, Robert Gordon, Teresa De Marco, Michael M Givertz, Alain Heroux, David Iklé, Judson Hunt, Abdallah G Kfoury, Joren C Madsen, Yvonne Morrison, Erika Feller, Sean Pinney, Sudipta Tripathi, Peter S Heeger, Randall C Starling
Clinical Trials in Organ Transplantation-18 (CTOT-18) is a follow-up analysis of the 200-subject multicenter heart transplant CTOT-05 cohort. CTOT-18 aimed to identify clinical, epidemiologic, and biologic markers associated with adverse clinical events past 1 year posttransplantation. We examined various candidate biomarkers including serum antibodies, angiogenic proteins, blood gene expression profiles, and T cell alloreactivity. The composite endpoint (CE) included death, retransplantation, coronary stent, myocardial infarction, and cardiac allograft vasculopathy...
December 14, 2018: American Journal of Transplantation
Branislav Kollar, Bohdan Pomahac, Leonardo V Riella
PURPOSE OF REVIEW: Vascularized composite allotransplantation (VCA) is a promising approach to restore the quality of life of carefully selected patients that suffered extensive injury. Although acute rejection occurs very frequently, still little is known about the specific characteristics of the VCA immune response. This review aims to highlight the current development in the field of VCA concerning the immunobiology and management of upper extremity and face transplant recipients. RECENT FINDINGS: T-cell mediated rejection is the predominant mechanism of allograft injury in VCA...
December 6, 2018: Current Opinion in Organ Transplantation
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
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