Vascularized Composite Allotransplantation最新文献

{"title":"Ex Vivo Primed Mesenchymal Stem Cell Therapy Prevents Endothelial Failure and Enhances Allograft Perfusion","authors":"Jessica B. Chang, Marc A. Soares, April M. Duckworth, Nakul Rao, Jonathan P. Massie, Camille Kim, Piul S. Rabbani, Daniel J Ceradini","doi":"10.4161/23723505.2014.970873","DOIUrl":"https://doi.org/10.4161/23723505.2014.970873","url":null,"abstract":"Endothelial failure following ischemia-reperfusion injury (IRI) in transplantation triggers the inflammatory cascade, compromising allograft perfusion and contributing to acute rejection. Culture conditions that activate the innate immunomodulatory phenotype of mesenchymal stem cells (MSCs) may attenuate IRI-mediated endothelial failure. We hypothesized that expansion in hypoxia or with inflammatory cytokines primes immunosuppressive functions of MSCs and improves allograft perfusion after ex-vivo delivery.","PeriodicalId":372758,"journal":{"name":"Vascularized Composite Allotransplantation","volume":"30 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2014-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"125721284","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":"The Impact of Skin Type and Area on Skin Rejection in Limb Transplantation","authors":"T. Hautz, D. Wolfram, N. Eberhart, H. Hackl, F. Messner, A. Weissenbacher, Michael Kimelman, B. Zelger, B. Zelger, S. Schneeberger","doi":"10.4161/23723505.2014.973795","DOIUrl":"https://doi.org/10.4161/23723505.2014.973795","url":null,"abstract":"Atypical manifestation of skin rejection observed in a series of hand transplant recipients suggests that appearance and mechanisms of rejection may vary and depend on skin type and location. We herein characterize skin rejection and inflammation at 3 defined areas of a rat hind-limb allograft. Allograft skin was harvested at the thigh, dorsum and planta pedis on postoperative day 5 and analyzed for histopathology, T-cell composition and expression of cytokines associated with skin inflammation. Isografts and naïve animals served as controls. Histology of the allograft skin collected on day 5 showed a diffuse cell infiltrate in the dermis and at the dermal-epidermal interface in the thigh and dorsum, whereas in the planta pedis it was mainly located perivascularly in the dermis. At all areas, epidermal involvement such as apoptotic keratinocytes and infiltrating lymphocytes were observed. Isograft skin showed only very mild or no signs of inflammation at all 3 locations. No significant difference was observed in the proportion of skin infiltrating CD45+CD3+CD4+ T-cells and CD45+CD3+CD8+ T-cells between the 3 sampling areas. Significant differences in cytokine protein expression were observed between hair bearing (thigh, dorsum) and hairless (planta pedis) skin, but not between the thigh and the dorsum (both hair bearing). MCP-1, IL-4, and GRO-KC exhibited the greatest individual expression at both locations thigh and dorsum in comparison with planta pedis. Differences in histopathologic appearance and cytokine expression in skin suggest area-specific mechanisms of rejection in a limb allograft, which should be considered for assessment and treatment of rejection.","PeriodicalId":372758,"journal":{"name":"Vascularized Composite Allotransplantation","volume":"13 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2014-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"121899783","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":"Discerning Rejection After Facial Allotransplantation by Utilization of Sentinel Flaps","authors":"Maximillian Kueckelhaus, S. Fischer, E. Bueno, C. Lian, G. Murphy, B. Pomahac","doi":"10.4161/23723505.2014.970046","DOIUrl":"https://doi.org/10.4161/23723505.2014.970046","url":null,"abstract":"Skin biopsies are critical for diagnosis and treatment of rejection after facial allotransplantation (FAT). Many facial allografts provide only limited skin area and frequent biopsies may compromise aesthetic outcome. In these cases, sentinel flaps (SFs), recovered as a free fasciocutanous radial forearm flap, have been employed for remote site rejection monitoring. These flaps maintain their axial blood supply similar to facial allografts (FA). The correlation between FA and SF in cases of rejection is presented.","PeriodicalId":372758,"journal":{"name":"Vascularized Composite Allotransplantation","volume":"77 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2014-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"126252937","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":"Inhibition of JAK/STAT Signaling Synergizes with CTLA4-Ig to Promote Transplant Survival","authors":"Madeline L. Fryer, S. Khalifian, B. Oh, Devin Miller, J. Budihardjo, W. Lee, G. Brandacher, G. Raimondi","doi":"10.4161/23723505.2014.970877","DOIUrl":"https://doi.org/10.4161/23723505.2014.970877","url":null,"abstract":"Murine T cell activation was assessed through a CFSE proliferation assay. Activation in an inflamed environment was simulated through addition of supernatant (MATSup) from maturing dendritic cells. Jak inhibition was exerted with the inhibitor Tofacitinib (Tofa). Differential expression of DC maturation markers in response to LPS C/¡ Tofa was analyzed by flow cytometry. In vivo synergism between Tofa and CTLA4-Ig was tested in B6 to BALB/c heart and skin graft models.","PeriodicalId":372758,"journal":{"name":"Vascularized Composite Allotransplantation","volume":"75 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2014-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"131693541","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":"Treatment with Local Anti-IL-1ß Prolongs Allograft Survival After Rat Vascularized Composite Allotransplantation","authors":"J. Grahammer, D. Moser, D. Wolfram, N. Eberhart, B. Zelger, B. Zelger, K. Kotsch, J. Pratschke, S. Schneeberger, T. Hautz","doi":"10.4161/23723505.2014.970886","DOIUrl":"https://doi.org/10.4161/23723505.2014.970886","url":null,"abstract":"Anti-IL-1b was applied in an experimental rat hindlimb transplantation model (Brown Norway (BN) rats to Lewis (LEW) rats). Four different treatment groups included: No treatment (1); baselineimmunosuppression consisting of FK506 30 mg/kg 50 days, ALS 0.5 mL day 0 C 3 (2), baseline immunosuppression C weekly injections of Anti-IL1b subcutaneously (s.c.) into the transplanted limb (3), baselineimmunosuppression C Anti-IL1b s.c. into the contralateral, nontransplanted limb (4). End-point was rejection grade III or postoperative day 100. Graft infiltrating cells were isolated and assessed for T cell populations using flow cytometry. Skin transplantations of BN and 3rd party rats were performed in long-survivors (> 100 days) to assess for tolerance.","PeriodicalId":372758,"journal":{"name":"Vascularized Composite Allotransplantation","volume":"22 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2014-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"128615143","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":"Post Transplantation High-dose Cyclophosphamide (PTCy) to Promote Immune Tolerance After Reconstructive Transplantation","authors":"G. Furtmüller, Madeline L. Fryer, S. Ganguly, J. Budihardjo, B. Oh, D. Cooney, G. Raimondi, W. Lee, L. Luznik, G. Brandacher","doi":"10.4161/23723505.2014.970908","DOIUrl":"https://doi.org/10.4161/23723505.2014.970908","url":null,"abstract":"The life-long use of immunosuppressants and their associated toxicities remains one of the primary obstacles that curtail the wider use of VCAs for reconstruction. In this study we therefore investigated if the combination of bone marrow transplantation and high dose cyclophosphamide induces a state of long term allograft acceptance in the setting of full thickness skin transplantation and orthotopic hind limb transplantation in a mouse model.","PeriodicalId":372758,"journal":{"name":"Vascularized Composite Allotransplantation","volume":"15 2 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2014-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"116920992","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":"Face Transplant Revisions: A Cautionary Endeavor","authors":"M. Sosin, R. Mohan, M. Fisher, A. Dorafshar, B. Bojovic, D. Gandhi, N. Iliff, E. Rodriguez","doi":"10.4161/23723505.2014.970035","DOIUrl":"https://doi.org/10.4161/23723505.2014.970035","url":null,"abstract":"Division of Plastic Surgery; R Adams Cowley Shock Trauma Center; University of Maryland School of Medicine; Baltimore, MD, USA; Department of Diagnostic Radiology and Nuclear Medicine; University of Maryland School of Medicine; Baltimore, MD, USA; Wilmer Eye Institute; Johns Hopkins School of Medicine; Baltimore, MD, USA; Department of Plastic Surgery; New York University Langone Medical Center; Institute of Reconstructive Plastic Surgery; New York, NY, USA","PeriodicalId":372758,"journal":{"name":"Vascularized Composite Allotransplantation","volume":"21 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2014-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"122612182","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":"Surgical and Logistical Aspects of Donor Limb Procurement in Hand and Upper Extremity Transplantation","authors":"O. Hausien, Edward W. Swanson, James A. Abraham, James P. Higgins, W. P. A. Lee, J. Shores, G. Brandacher","doi":"10.4161/23723505.2014.973799","DOIUrl":"https://doi.org/10.4161/23723505.2014.973799","url":null,"abstract":"Hand and upper extremity transplantation offers a promising reconstructive solution for select patients lacking a functional upper limb. For such an endeavor, it is imperative that multiple medical and surgical specialties and teams work in concert to achieve a common goal. Sixteen years from the first successful hand transplantation, the number of centers performing or planning to perform hand transplantation worldwide has increased considerably. This procedure may become the standard of care for properly selected patients in the not-too-distant future. To facilitate this transition, unified protocols are required. In this manuscript, we focus on the donor limb procurement process, including the sequence of events, logistics, and inter-specialty team interaction. Through review of the current literature, we acknowledge and address possible variations, and provide an illustrative overview of the operation. It is important that all members involved in this procedure, including the Organ Procurement Organization (OPO), solid organ procurement teams, and donor hospital staff, are aware of this process. Opportunities for future research in this field are further discussed.","PeriodicalId":372758,"journal":{"name":"Vascularized Composite Allotransplantation","volume":"331 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2014-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"122840284","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":"Anatomy of an Error","authors":"T. Starzl","doi":"10.4161/23723505.2014.975039","DOIUrl":"https://doi.org/10.4161/23723505.2014.975039","url":null,"abstract":"It has been a particular pleasure to see the life-changing impact of the hand, face, and other composite allografts. Over the past decade, a rapidly growing number of this novel type of transplants have been performed worldwide with highly encouraging functional and immunological outcomes. Recipients of these grafts represent a new generation of transplant recipient pioneers. The uniqueness of their grafts, which include donor bone and its marrow, could help further elucidate the mechanisms by which transplanted organs and tissues are accepted. In turn, novel strategies to facilitate these mechanisms may be developed. The title of my talk today could be improved. A more explanatory title would be “The missing half of the Billingham-Brent-Medawar discoveries.\" This informational void caused a pervasive early error that precluded the orderly development of transplantation immunology and limited clinical progress almost exclusively to the development of more potent immunosuppressive drugs. To understand how an error of this magnitude could have occurred, it is necessary to go back to the birth of modern day transplantation. The midwife was the English Zoologist, Peter Medawar. The seed from which all else derived was Medawar’s demonstration in 1943 that skin graft rejection is an immunologic event. In the next 10 years, efforts to weaken the immune response with irradiation or steroids had little or no effect on experimental graft survival. During the same period, however, a study by Medawar’s team of the natural tolerance in freemartin cattle revealed a chink in the immunologic armor. In freemartin cattle, fusion of their placentas allowed mixture of the 2 animal circulations during gestation. After birth and throughout life, the animals shared each others blood cells (blood chimerism). Moreover, the cattle were tolerant to each others tissues and organs. Inspired by the freemartin findings, Medawar and his colleagues demonstrated in 1953 that similar chimerism-associated tolerance could be deliberately produced. In their experimental model, splenic or bone marrow leukocytes were infused from adult mouse donors into newborn mouse recipients whose immune system was not developed enough to reject the cells. With leukocyte engraftment, the neonatal recipients had lifetime tolerance to skin (or other tissues) from the original leukocyte donor, but not to tissues from any other donor. These chimeric mice were analogs of future patients treated with bone marrow transplantation for immune deficiency diseases. In 1956, Main and Prehn at the NIH extended these observations to adult mouse recipients whose fully competent immune system had been weakened with high dose total body irradiation before the cell infusion. These mouse chimeras were analogs of today’s cytoablated human bone marrow recipients. Stable donor leukocyte chimerism in both mouse models was achievable only when the donors and recipients had a good histocompatibility match. Otherwise, the don","PeriodicalId":372758,"journal":{"name":"Vascularized Composite Allotransplantation","volume":"244 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2014-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"131570253","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":"MHC Class I Matching Between Donors and Recipients Influences the Skin Tolerance of Vascularized Composite Allografts","authors":"K. Shanmugarajah, D. Leonard, C. Mallard, H. Powell, A. Albritton, M. Randolph, E. Harrington, D. Sachs, J. Kurtz, C. Cetrulo","doi":"10.4161/23723505.2014.970912","DOIUrl":"https://doi.org/10.4161/23723505.2014.970912","url":null,"abstract":"The development of VCA tolerance protocols would obviate the need for chronic immunosuppression and allow widespread use of this highly promising reconstructive modality. However, achieving robust tolerance of the skin component of VCAs has proven particularly challenging in pre-clinical large animal models. Our laboratory has recently reported acceptance of VCAs (>600 d), including the skin component, across a haploidentical MHC barrier in a miniature swine model using a mixed chimerism approach. In this study, we investigated whether sharing of MHC class I and/ or class II between donor and recipient influences skin tolerance.","PeriodicalId":372758,"journal":{"name":"Vascularized Composite Allotransplantation","volume":"54 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2014-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"115286560","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}