Vascularized Composite Allotransplantation最新文献

{"title":"2544: Patient recruitment and referral patterns in face transplantation","authors":"H. Kiwanuka, M. Aycart, E. Bueno, M. Alhefzi, N. Krezdorn, B. Pomahac","doi":"10.1080/23723505.2016.1232968","DOIUrl":"https://doi.org/10.1080/23723505.2016.1232968","url":null,"abstract":"2544: Patient recruitment and referral patterns in face transplantation Harriet Kiwanuka, Mario A. Aycart, MD, Ericka Bueno, Muayyad Alhefzi, Nicco Krezdorn, and Bohdan Pomahac Brigham and Women’s Hospital, Boston, MA, USA Promising short term results raise an important question regarding its patient population—are centers that perform face transplantation effectively reaching individuals from the targeted facial disfigurement population? Our center reviewed our face transplantation contacts to assess patient recruitment and outreach performance. Methods We performed a retrospective review of subjects who requested screening for face transplantation (aka: “Contacts”) between the time of our IRB protocol approval (February 2008) to October 2015. We investigated the relationship between referral mode (physician vs self) with the Contact’s demographic characteristics (age, gender, race, mechanism of injury, geographic location) and clinical trial status. Results There were a total of 72 face transplantation Contacts The average age of the Contacts was 38 years, and the majority of them were male (n D 41, 569%) The predominant race of Contacts was White (n D 33) and the most prevalent mechanism of injury was burns (n D 32) The majority of our Contacts resided within the US (n D 47), with the majority from the Northeastern US (n D 21) Of the 72 Contacts, 35 (486%) were physician referrals and 37 (514%) were self referrals Physician referrals led to the most screened and transplanted Contacts in our center, whereas self-referral often led to immediate exclusion. Conclusions In this study, we show the diversity of patient characteristics and referral patterns in our clinical trial Furthermore, we describe the relationship of characteristics to outcomes in our cohort and identify areas of improvement, such as patient and physician education. Lastly, we are reminded of face transplantation’s potential impact. Figure 1. Overall clinical status of contacts -no (%). CONTACT Harriet Kiwanuka hkiwanuka@partners.org © 2016 Harriet Kiwanuka, Mario A. Aycart, Ericka Bueno, Muayyad Alhefzi, Nicco Krezdorn, and Bohdan Pomahac. Published with license by Taylor & Francis. This is an Open Access article distributed under the terms of the Creative Commons Attribution-Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. The moral rights of the named author(s) have been asserted. VASCULARIZED COMPOSITE ALLOTRANSPLANTATION 2016, VOL. 3, NOS. 1–2, 30 http://dx.doi.org/10.1080/23723505.2016.1232968","PeriodicalId":372758,"journal":{"name":"Vascularized Composite Allotransplantation","volume":"7 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2016-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"114992276","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"2546: Non-cytoreductive immunosuppression prevents rejection of vascularized composite allografts","authors":"B. Oh, G. Furtmuller, M. Iglesias, Madeline L. Fryer, G. Raimondi, D. Cooney, W. Lee, G. Brandacher","doi":"10.1080/23723505.2016.1232969","DOIUrl":"https://doi.org/10.1080/23723505.2016.1232969","url":null,"abstract":"2546: Non-cytoreductive immunosuppression prevents rejection of vascularized composite allografts Byoung Chol Oh, DVM, PhD, Georg Furtmuller, MD, Marcos Iglesias, PhD, Madeline Fryer, BS, Giorgio Raimondi, PhD, Damon Cooney, MD, PhD, W. P. Andrew Lee, MD, and Gerald Brandacher, MD Johns Hopkins University School of Medicine, Vascularized Composite Allotransplantation (VCA) Laboratory, Baltimore, MD, USA Background Reconstructive transplantation represents a valid therapeutic option after devastating tissue loss such as an extremity or face Immunosuppression-free donorspecific immunological tolerance has been successfully achieved in the setting of solid organ transplantation through mixed chimerism Routine clinical application of this approach, however, is hampered by the toxicity of the cytoreductive recipient conditioning The current study investigated a novel non-cytoreductive immunosuppressive strategy in a murine model of hind limb transplantation. Methods Fully MHC-mismatched allogeneic, orthotopic hind limb transplants were performed from Balb/C to C57BL/6 mice Recipient animals in the experimental groups received no treatment (Group 1); 025 mg CTLA4 Ig on postoperative days (POD) 0, 2, 4, and 6 (Group 2); 20 mg/kg anti-T cells (anti-Thy 12 mAb) on POD-1 plus CTLA4-Ig and 1 mg/kg Rapamycin (POD0-9) (Group 3) Flow cytometric analysis was performed to evaluate mixed chimerism and clonal deletion of alloreactive T cells. Results The CTLA4 Ig treated group showed increased graft survival compared to non-treated controls (mean survival time [MST] 17 d and 8 d, respectively, p < 001) Interestingly, combination of T cell depletion and CTLA4 Ig plus short-course of Rapamycin increased VCA survival significantly (MST 105 days; p < 001) Donor derived mixed chimerism was detected in recipients receiving the combined treatment protocol with 50 § 12 % of donor derived CD11bC cells on POD 55 VÎ – TCR staining profiles in recipients after combined treatment showed 16 § 04 % of Î=2Î25CCD4C T cells, while nae Ave C57BL/6 express 36 § 04 % of Î=2Î 25CCD4C T cells, suggesting central deletion of donor-reactive T cells Also, we found infiltrating Foxp3C regulatory T cells expressing donor derived marker (H-2K) at POD60 on combined treatment representing donor derived T reg cells were infiltrated. Conclusion This study shows that combination of T cell depletion and costimulation blockade and short-course of Rapamycin prevents VCA rejection and significantly prolongs graft survival Also, these data show that a clinically acceptable non-cytoreductive strategy could be applied in VCA to avoid long-term maintenance immunosuppression. CONTACT Gerald Brandacher, MD gbranda2@jhmi.edu © 2016 Byoung Chol Oh, Georg Furtmuller, Marcos Iglesias, Madeline Fryer, Giorgio Raimondi, Damon Cooney, W. P. Andrew Lee, and Gerald Brandacher. Published with license by Taylor & Francis. This is an Open Access article distributed under the terms of the Creative Commons Attribution","PeriodicalId":372758,"journal":{"name":"Vascularized Composite Allotransplantation","volume":"107 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2016-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"123240040","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"2519: Development of de novo donor-specific HLA antibodies after combined intestinal and vascularized composite allotransplantation","authors":"A. Weissenbacher, G. Vrakas, Mian Chen, S. Reddy, S. Fuggle, P. Friend","doi":"10.1080/23723505.2016.1232937","DOIUrl":"https://doi.org/10.1080/23723505.2016.1232937","url":null,"abstract":"2519: Development of de novo donor-specific HLA antibodies after combined intestinal and vascularized composite allotransplantation Annemarie Weissenbacher, MD, Georgios Vrakas, Mian Chen, Srikanth Reddy, Susan Fuggle, and Peter Friend Oxford Transplant Centre, Oxford, UK Background In the young field of VCA as well as in bowel and multivisceral transplantation, the occurrence of DSA has been described Our aim was to investigate the incidence and clinical effect of de novo (dn) DSA in our cohort of patients receiving an intestinal transplant together with a vascularised abdominal wall graft Methods This is a single-center, retrospective clinical study The patient cohort includes all recipients of deceased donor intestinal and VCA transplants performed at the Oxford Transplant Centre between October 2008 and December 2015 Pre-transplant HLA antibody status was available for all patients Results Thirty-two intestinal transplants were included One patient underwent a second small bowel and abdominal wall transplant All organs were retrieved from DBD donors There were 8 modified multivisceral transplants (8/32, 25%) and 24 isolated small bowel transplants (24/32, 75%) An abdominal wall (from the same donor) was used in 18 cases (18/32, 56%) All patients received alemtuzumab induction and tacrolimus maintenance immunosuppression DSA were detectable in 2/31 (65%) recipients before the combined transplant Twelve (387%), of the remaining 29, developed dnDSA Five patients developed dnDSA against HLA class-I (156%), 4 against classII (125%) and 3 (94%) against both classes The mean MFI was 3094 § 5642 SD In the VCA group, a lower percentage developed dnDSA compared to the group without VCA; 6/14 (429%) vs 6/18 (33%) Intestinal rejection was proven in 5/14 (357%) cases without VCA and 3/18 (167%) cases with the VCA VCA rejection was seen in 7/18 (389%) cases One was grade 1, 1 grade 2 and 5 grade 3 There were no episodes of intestinal rejection without VCA rejection The occurrence of dnDSA in the absence of clinical rejection has not led to organ or patient deterioration and has not been treated Conclusion The combination of intestinal transplantation with a VCA is immunologically complex: although we have found no evidence that the VCA sensitizes the patient, predisposing to rejection of both organs, further experience is needed Our data suggest that combining an abdominal wall VCA with an intestinal transplant does not increase the incidence of dnDSA. CONTACT Annemarie Weissenbacher, MD annemarie.weissenbacher@nds.ox.ac.uk © 2016 Annemarie Weissenbacher, Georgios Vrakas, Mian Chen, Srikanth Reddy, Susan Fuggle, and Peter Friend. Published with license by Taylor & Francis. This is an Open Access article distributed under the terms of the Creative Commons Attribution-Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work ","PeriodicalId":372758,"journal":{"name":"Vascularized Composite Allotransplantation","volume":"9 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2016-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"125268403","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"2561: Dynamics and correlates of skin dendritic cells with distinctive immune response profiles in vascularized composite allografts","authors":"Wensheng Zhang, Chiaki Komatsu, F. Feturi, Lin He, Liwei Dong, Jiaqing Wu, M. Miller, J. Walch, A. Mathers, A. Thomson, K. Washington, V. Gorantla, M. Solari","doi":"10.1080/23723505.2016.1233011","DOIUrl":"https://doi.org/10.1080/23723505.2016.1233011","url":null,"abstract":"2561: Dynamics and correlates of skin dendritic cells with distinctive immune response profiles in vascularized composite allografts Wensheng Zhang, MD, PhD, Chiaki Komatsu, MD, Firuz Gamal Feturi, BPharm, PhD, Lin He, MD, Liwei Dong, Jiaqing Wu, MD, PhD, Maxine Reedy Miller, MD, Jeffrey Mark Walch, MD/PhD, Alicia Mathers, PhD, Angus W. Thomson, Kia M. Washington, MD, Vijay Gorantla, and Mario Solari University of Pittsburgh, Pittsburgh, PA, USA Introduction Vascularized composite allografts (VCA) such as hand allografts, contains large amount of most immunogenic skin component Multiple acute rejection episodes in the majority of human VCA routinely target skin while sparing other tissue types Skin dendritic cells (DCs) are thought to play critical roles in either initiation or regulation of skin immunity However, their contribution to the unique alloimmune response and acute skin rejection of VCA is still largely unknown This study seeks to characterize the spatiotemporal dynamics of skin resident DCs at different stages of rejection after hind-limb transplantation and to better understand the role of skin DCs in immunomodulation of VCA. Materials and methods Lewis rats received allogeneic hind-limb transplants from BN rats without immunosuppressive treatment, and were inspected daily for their clinical signs of rejection using a visual scoring system Recipients were sacrificed at different time points post-transplantation Allograft skin, adjacent recipient skin, and draining lymph nodes were harvested and processed to obtain single cell suspension for flow cytometric analysis, or to extract total RNA and proteins and assessed by real-time PCR and Luminex. Results 1) We developed a new technique for isolation and characterization of skin DCs in rat hind-limb transplant model 2) Skin resident lymphocytes and distinct subsets of skin migratory DCs: Langerhans cells (LCs), dermal DCs (DDCs), and langerinC DDCs, in the transplanted limb were identified and enumerated 3) Skin migratory DCs in both allograft and recipient limb skin showed different patterns of change with increasing severity of rejection 4) The expression of Th1-, Th2-, Th17-, and Tregassociated genes and cytokines in allograft and recipient limb skin exhibited dynamic changes and temporal correlation with the quantity of skin DCs during the process of rejection. Conclusions The correlative trends between skin DC subsets and T cell-mediated alloimmune response suggest a complex cutaneous immune cell network modulated by skin DCs in VCA By understanding the dynamics of skin DCs and their influence on the T-cell response, the novel targeted immunomodulation therapy can be developed for VCA. Funding This work was supported by American Association of Plastic Surgeons Academic Scholarship. CONTACT Mario Solari solarimg@upmc.edu © 2016 Wensheng Zhang, Chiaki Komatsu, Firuz Gamal Feturi, Lin He, Liwei Dong, Jiaqing Wu, Maxine Reedy Miller, Jeffrey Mark Walch, Alicia Mathers, Angus W. Thomson","PeriodicalId":372758,"journal":{"name":"Vascularized Composite Allotransplantation","volume":"48 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2016-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"114894174","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"2560: Outcomes of solid organ transplants following simultaneous solid organ and vascularized composite allograft procurements: A nationwide analysis","authors":"M. Aycart, M. Alhefzi, G. Sharma, N. Krezdorn, E. Bueno, S. Talbot, M. Carty, S. Tullius, B. Pomahac","doi":"10.1080/23723505.2016.1234221","DOIUrl":"https://doi.org/10.1080/23723505.2016.1234221","url":null,"abstract":"2560: Outcomes of solid organ transplants following simultaneous solid organ and vascularized composite allograft procurements: A nationwide analysis Mario A. Aycart, MD, Muayyad Alhefzi, MD, Gaurav Sharma, MD, Nicco Krezdorn, MD, Ericka M. Bueno, PhD, Simon G. Talbot, MD, Matthew J. Carty, MD, Stefan G. Tullius, MD, PhD, and Bohdan Pomahac, MD Brigham and Women’s Hospital, Boston, MA, USA Background Current knowledge of the impact of facial vascularized composite allograft (VCA) procurement on the transplantation outcomes of the concomitantly recovered solid organs is limited to isolated case reports and short-term results. Here we report on a nationwide analysis of facial allograft donor surgery experience and long-term outcomes of the concomitantly recovered solid organs and their recipients. Methods There were 10 facial VCA procurements between December 2008 and October 2014. We identified the population of subjects who received solid organs from these 10 donors using the Scientific Registry of Transplant Recipients. We retrospectively reviewed operative characteristics, intra-operative parameters, and postoperative outcomes. Results Six of 10 donor surgeries were performed at outside institutions, all on brain-dead donors. Mean operative duration for facial VCA recovery was 69 hours (range 4 – 1325 hours). A total of 36 solid organs were recovered and transplanted into 35 recipients. Survival rates for kidney and liver recipients were 100 and 90% at a median follow-up of 33 and 275 months, respectively (range, 6–72 months). Graft survival rates for kidneys and livers were 15/16 (94%) and 9/10 (90%), respectively. Recipient and graft survival rates for hearts and lungs were 75% (nD 4) and 100% (nD 3) at mean follow-up time of 1475 and 16 months, respectively. Conclusions The advent and continued progress of vascularized composite allotransplantation has ushered in a new clinical arena in the field of transplantation. Critical to its advancement is the planning and safe execution of the donor procurement. Despite logistical and technical variation, we show that the procurement of facial VCA and simultaneous upper extremities does not appear to adversely affect the outcomes of transplant recipients of concomitantly recovered solid organs. Excellent coordination and communication between the organ recovery teams remains paramount with guidance and support from the respective organ procurement organization. CONTACT Mario A. Aycart maycart@partners.org © 2016 Mario A. Aycart, Muayyad Alhefzi, Gaurav Sharma, Nicco Krezdorn, Ericka M. Bueno, Simon G. Talbot, Matthew J. Carty, Stefan G. Tullius, and Bohdan Pomahac. Published with license by Taylor & Francis. This is an Open Access article distributed under the terms of the Creative Commons Attribution-Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is proper","PeriodicalId":372758,"journal":{"name":"Vascularized Composite Allotransplantation","volume":"235 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2016-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"122670688","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"2531: Cervical lymph node transplantation model in rats","authors":"Ş. Uygur, C. Ozturk, M. Bozkurt, G. Kwiecien, M. Madajka, M. Siemionow","doi":"10.1080/23723505.2016.1234252","DOIUrl":"https://doi.org/10.1080/23723505.2016.1234252","url":null,"abstract":"2531: Cervical lymph node transplantation model in rats Safak Uygur, Can Ozturk, Mehmet Bozkurt, Grzegorz Kwiecien, Maria Madajka, and Maria Siemionow Department of Orthopaedics, University of Illinois at Chicago, College of Medicine, Chicago, IL, USA; Cleveland Clinic, Cleveland, OH, USA Introduction Over the past decade, there was an interest in the role of lymph node transplantation for tolerance induction in VCA. Currently, there are only few experimental small animal models of vascularized lymph node transplantation. Thus, reliable rodent models are needed to further investigate the mechanism and immunological impact of vascularized lymph node transplantation in the context of VCA. In this study we are introducing the vascularized cervical lymph node flap as a new model for transplantation studies. Methods Ten male Sprague-Dawley rats weighing 200 to 250 g were used in this study. The anatomic features of the cervical lymph nodes were explored. Anatomic dissections were performed and lymph node containing flaps were harvested from the cervical region based on the common carotid artery and jugular vein. Methylene blue dye was injected into the arterial pedicle. Lymph nodes were identified, and their structures was confirmed by histological evaluation. Indocyanine-green angiography was used to confirm perfusion of the lymph node flap. Results The length of the vascular pedicle was in a range between 2.5 to 3 cm. Adequate methylene blue dye perfusion and venous perfusion were observed in the flap after injection. The dye disseminated evenly and stained all lymph nodes included in the flap, confirming that the harvested lymph node flap has a wellestablished vascular network. There were 5 to 6 lymph nodes observed in the single flap. Perfusion of the flaps was demonstrated by indocyanine-green angiography. Conclusions To the best of our knowledge this is the first study describing the vascularized cervical lymph node flap in rats. We have demonstrated good flap perfusion by indocyanine-green angiography and confirmed the presence of a high number of lymph nodes (5–6) per flap. This cervical lymph node flap can be used for different applications including transplantation and lymphedema studies as well as studies testing mechanism of immunological tolerance induction and rejection. CONTACT Safak Uygur safakuygur@gmail.com © 2016 Safak Uygur, Can Ozturk, Mehmet Bozkurt, Grzegorz Kwiecien, Maria Madajka, and Maria Siemionow. Published with license by Taylor & Francis. This is an Open Access article distributed under the terms of the Creative Commons Attribution-Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. The moral rights of the named author(s) have been asserted. VASCULARIZED COMPOSITE ALLOTRANSPLANTATION 2016, VOL. 3, NOS. 1–2, 41 http://dx.doi.org/10.1080/23723505.2016.1234252","PeriodicalId":372758,"journal":{"name":"Vascularized Composite Allotransplantation","volume":"36 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2016-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"122737624","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"2558: Optimization of intra-thymic transplantation of donor-derived thymic epithelial cells to promote lasting regulation of anti-donor reactivity","authors":"Sara AlFadil, Kim Mi-jeong, Marcos Iglesias Lozano, B. Oh, W. Lee, G. Brandacher, Thomas Serworld, G. Raimondi","doi":"10.1080/23723505.2016.1234206","DOIUrl":"https://doi.org/10.1080/23723505.2016.1234206","url":null,"abstract":"2558: Optimization of intra-thymic transplantation of donor-derived thymic epithelial cells to promote lasting regulation of anti-donor reactivity Sara Alfadil, Kim Mi-Jeong, Marcos Iglesias Lozano, Byoung Chol Oh, W. P. Andrew Lee, Gerald Brandacher, Thomas Serworld, and Giorgio Raimondi Johns Hopkins University School of Medicine, Vascularized Composite Allotransplantation (VCA) Laboratory, Baltimore, MD; Joslin Diabetes Center, Boston, MA, USA Background Targeting the process of central (thymic) selection of developing T lymphocytes is the key mechanism for transplant tolerance induction mediated bybone marrow transplantation (BM-Tx)-based protocols. However, they are not amenable to most transplant recipients. Thymic Epithelial Cells (TEC), a population of stromal cells residing in the thymus, exert a major contribution to central selection. Unfortunately, donor TEC do not develop following BM-Tx protocols. Therefore, we propose a new strategy that voids the need for heavy pre-conditioning and is based on generating a donor-recipient “Hybrid Thymus,” through donor TEC engraftment, to re-engineer the thymic microenvironment and promote lasting central tolerance. Methods We developed an improved protocol for isolating mouse TEC via a combination of negative and positive selection. Allogeniec (Allo)-TEC purified from BALB/c were injected into the right thymic lobe of C57BL/6, Recipients were divided in groups based on treatment with CTLA4-Ig C/¡ anti-CD40L C/¡ T depletion. 14, 28, and 45 days post-injection Allo-TEC survival was assessed and the selection and reactivity of T cells was analyzed via flow cytometry and CFSEbased mixed lymphocyte reaction. Results Our optimized purification protocol yields an average 70% TEC purity. Unmanipulated recipients promptly rejected Allo-TEC, indicating the existence of effective immunity in the thymus. However, CTLA4-Ig and MR1 co-administration exerted a significant (but not lasting) protection. In this latter group, the percentage of peripheral Vb11C T cells (inversely correlated with central selection) on d24 was significantly lower, indicating functional activity of the engrafted donor TEC. Addition of transient T depletion enabled longterm engraftment of Allo-TEC that, on d45, were in a normal architecture within the thymus integrated with recipient thymocytes. However, antidonor T cell reactivity remained unaltered, suggesting the need for engraftment in both thymic lobes for proper regulation. Conclusion Our preliminary data show that the thymic engraftment, survival, and function of allo-TEC can be promoted via costimulation blockade C T depletion. These exciting results indicate that engineering a donor-recipient Hybrid Thymus is feasible and has the potential to promote a dominant regulation of alloreactivity that could be conducive to transplant tolerance induction. CONTACT Sara Alfadil salfadi1@jhmi.edu © 2016 Sara Alfadil, Kim Mi-Jeong, Marcos Iglesias Lozano, Byoung Chol Oh, W. P. Andrew Lee,","PeriodicalId":372758,"journal":{"name":"Vascularized Composite Allotransplantation","volume":"19 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2016-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"133498611","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Systematic pathological component scores for skin-containing vascularized composite allografts","authors":"I. Rosales, R. Foreman, M. DeFazio, D. Sachs, C. Cetrulo, D. Leonard, R. Colvin","doi":"10.1080/23723505.2017.1318200","DOIUrl":"https://doi.org/10.1080/23723505.2017.1318200","url":null,"abstract":"ABSTRACT Clinical management of skin-containing vascularized composite allografts (VCA) requires accurate assessment of the graft status, typically based on skin biopsies. The Banff 2007 Working Classification proposed 4 grades of acute rejection, but did not score individual features or include vascular rejection. Here we report a systematic scoring system developed from MHC-mismatched porcine skin-containing VCA. Biopsies from 20 VCA, 9 autologous skin flaps and 9 normal skin were analyzed to optimize the methodology and set thresholds. The components quantified were: perivascular cells/dermal vessel (pc), perivascular dermal infiltrate area (pa), luminal leukocytes/capillary or venule (c), epidermal infiltrate (ei), epidermal apoptosis or necrosis (e), endarteritis (v), and chronic allograft vasculopathy (cav). To evaluate prognostic value, we scored a separate group of 28 serial biopsies from 8 recipients (4 that were ultimately accepted and 4 that rejected. Parameters on the initial biopsies predicting later graft rejection included pc (p < 0.02), pa (p < 0.03), ei (p < 0.0005), e (p < 0.003) and c (p < 0.005). Reproducibility between 2 pathologists blinded to clinical data was acceptable, with weighted kappa scores for pc (0.673), pa (0.399), ei (0.464), e (0.663), v (0.766), and c (0.642). This component scoring system can be adapted clinically, since human and porcine skin are highly similar. Vascular lesions in VCA are also highlighted in this system and could impact graft outcome. The component score approach complements Banff 2007 grades and will enable the establishment of clinically significant thresholds.","PeriodicalId":372758,"journal":{"name":"Vascularized Composite Allotransplantation","volume":"214 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2016-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"123558678","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"2549: Results of a survey of organ procurement organizations to identify barriers to VCA authorization and recovery in the US","authors":"W. Cherikh, A. Harper, R. Luskin, Christopher L Wholley, S. McDiarmid","doi":"10.1080/23723505.2016.1232979","DOIUrl":"https://doi.org/10.1080/23723505.2016.1232979","url":null,"abstract":"","PeriodicalId":372758,"journal":{"name":"Vascularized Composite Allotransplantation","volume":"54 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2016-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"126494601","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"2526: Non-invasive monitoring of allograft rejection using thermal imaging in a large animal model of vascularized composite allotransplantation","authors":"K. Kolegraff, A. Quan, Nicole J. Crane, Howard D. Wang, Joseph Lopez, G. Furtmuller, Sara AlFadil, S. Mermulla, B. Oh, Paul J. Akre, Jose C. Alonso-Escalante, J. Walch, J. Shores, D. Cooney, S. Bonawitz, E. Elster, G. Brandacher, W. Lee","doi":"10.1080/23723505.2016.1234260","DOIUrl":"https://doi.org/10.1080/23723505.2016.1234260","url":null,"abstract":"2526: Non-invasive monitoring of allograft rejection using thermal imaging in a large animal model of vascularized composite allotransplantation Keli Kolegraff, Amy Quan, Nicole Crane, Howard Wang, Joseph Lopez, Georg Furtmuller, Sara Alfadil, Sara Mermulla, Byoung Chol Oh, Paul Akre, Jose C. Alonso-Escalante, Jeffrey Walch, Jaimie Shores, Damon Cooney, Steven Bonawitz, Eric Elster, Gerald Brandacher, and W. P. Andrew Lee Johns Hopkins University School of Medicine, Baltimore, MD, USA; Naval Medical Research Center, Bethesda, MD, USA; Uniformed Services University of the Health Sciences and Walter Reed National Military Medical Center, Bethesda, MD, USA Background Vascularized composite allotransplantation (VCA), including hand and face transplantation, is increasingly utilized for reconstruction of disfiguring injuries. Immune rejection is a problem inherent to allotransplantation and must be recognized early to prevent graft injury/loss. Skin biopsy is required to confirm rejection however this approach may further promote rejection through tissue injury. Thermal imaging has been used to non-invasively detect inflammation and ischemia in other disease states but has not been evaluated in VCA rejection. The purpose of this study was to evaluate the utility of non-invasive thermal imaging in the detection of rejection in a swine VCAmodel. Methods Osteomyocutaneous hindlimb transplantation was performed in 9 MGH miniature swine across a full SLA mismatch. The positive rejection control group (3 pigs) did not receive any form of immunosuppression. The treated group (6 pigs) received non-myeloablative conditioning with 50cGy total body and 350cGy thymic irradiation prior to transplantation, daily tacrolimus (20–25 ng/ml) until POD 30, and IV steroids on POD 4–6. Allografts were assessed daily for erythema, edema, blistering, and ulceration. Daily infrared images were acquired using a thermal camera (FLIR E8 #63903-0303) and thermal emission intensities from graft and contralateral flank control were analyzed using Image. Results In the untreated group, erythema was observed by POD 4 and progressed to epidermolysis by POD 8 in 3/3 animals. In the treated group, rejection was observed at POD 5–7 in 6/6 animals and was reversed by POD 10 with steroids in 5/6 animals. The sixth animal developed severe rejection on POD 5 that progressed to necrosis despite steroids. Interestingly, infrared imaging did not distinguish these episodes of rejection in the early post-operative period (<POD 30) despite clinical signs of inflammation and biopsyproven rejection (Banff II–IV). At later post-operative periods (>POD 60), there was a trend toward cooler graft temperatures even in the absence of clinical rejection. Conclusions Despite signs of inflammation, infrared imaging did not reliably detect graft rejection. The finding that grafts become cooler over time suggests there may be long-term changes in graft perfusion. This may represent chronic graft injury and is ","PeriodicalId":372758,"journal":{"name":"Vascularized Composite Allotransplantation","volume":"363 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2016-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"121379475","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}