C. Cakmakoglu, B. Gharb, A. Rampazzo, G. Kwiecien, M. Madajka, Addison Barnett, F. Papay
{"title":"2499: Establishing a novel surgical model for optic nerve repair","authors":"C. Cakmakoglu, B. Gharb, A. Rampazzo, G. Kwiecien, M. Madajka, Addison Barnett, F. Papay","doi":"10.1080/23723505.2016.1234214","DOIUrl":"https://doi.org/10.1080/23723505.2016.1234214","url":null,"abstract":"2499: Establishing a novel surgical model for optic nerve repair Cagri Cakmakoglu, MD, Bahar Bassiri Gharb, MD, PhD, Antonio Rampazzo, MD, PhD, Grzegorz Kwiecien, MD, Maria Madajka, PhD, Addison Barnett, BS, and Francis Papay, MD Cleveland Clinic, Cleveland, OH, USA; Plastic Surgery, Cleveland, OH, USA Background Efforts to transplant a mammalian eye have failed mainly due to the ganglion cell axon’s inability to withstand transection. Eye transplantation is not feasible without proof of optic nerve regeneration. The objective of this pilot study is to find an optimal rat optic nerve transection and repairmodel in preparation for eye transplantation. Methods 30 cadaver and 10 live Lewis rats were used to expose, transect, and repair the optic nerve and visualize its anatomical relationship with the ophthalmic artery. Nerve coaptation was performed with 12/0 suture. The pathway of the ophthalmic artery was evaluated by red latex injection.","PeriodicalId":372758,"journal":{"name":"Vascularized Composite Allotransplantation","volume":"38 11","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2016-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"113970244","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}
Ewa Bryndza Tfaily, M. Cyran, R. Gendek, E. Szilagyi, Jason L Le, A. Domaszewska-Szostek, J. Cwykiel, M. Siemionow
{"title":"2594: In vitro and in vivo characterization of human hematopoietic chimeric cells - A novel strategy to induce tolerance in transplantation","authors":"Ewa Bryndza Tfaily, M. Cyran, R. Gendek, E. Szilagyi, Jason L Le, A. Domaszewska-Szostek, J. Cwykiel, M. Siemionow","doi":"10.1080/23723505.2016.1234208","DOIUrl":"https://doi.org/10.1080/23723505.2016.1234208","url":null,"abstract":"2594: In vitro and in vivo characterization of human hematopoietic chimeric cells A novel strategy to induce tolerance in transplantation Ewa Bryndza Tfaily, PhD, Malgorzata Cyran, MD, Rafal Gendek, MD, PhD, Erzsebet Szilagyi, MD, PhD, Jason Le, MD, Anna Domaszewska-Szostek, PhD, Joanna Cwykiel, MSc, and Maria Siemionow, MD, PhD, DSc University of Illinois at Chicago, Chicago, IL, USA; Polish Academy of Science, Warszawa, Poland Background Cell-based therapies represent a new promising approach for tolerance induction in transplantation One of the methods for immune response modulation in solid organ and vascularized composite allograft (VCA) recipients is donor bone marrow (BM) transplantation We propose a new cellular therapy based on application of the ex vivo created donor-recipient chimeric cells as an alternative approach to BM-based therapies in support of solid organ and VCA transplantation The aim of this study was further characterization of human hematopoietic chimeric cells (HHCC).","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":"121336993","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}
Howard D. Wang, S. Fidder, Devin Miller, G. Furtmuller, D. Lough, Joseph Lopez, A. Quan, J. Budihardjo, G. Raimondi, Zhaoli Sun, W. Lee, G. Brandacher
{"title":"2578: Improved vascularized composite allograft survival in sensitized rats after syngeneic hematopoietic stem cell transplantation and fludarabine","authors":"Howard D. Wang, S. Fidder, Devin Miller, G. Furtmuller, D. Lough, Joseph Lopez, A. Quan, J. Budihardjo, G. Raimondi, Zhaoli Sun, W. Lee, G. Brandacher","doi":"10.1080/23723505.2016.1233023","DOIUrl":"https://doi.org/10.1080/23723505.2016.1233023","url":null,"abstract":"2578: Improved vascularized composite allograft survival in sensitized rats after syngeneic hematopoietic stem cell transplantation and fludarabine Howard D. Wang, MD, Samuel Fidder, MD, Devin Miller, MD, Georg Furtmuller, MD, Denver M. Lough, MD, PhD, Joseph Lopez, MD, MBA, Amy Quan, MPH, Joshua Budihardjo, Giorgio Raimondi, PhD, Zhaoli Sun, 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 Vascularized composite allotransplantation (VCA) is a promising option for patients with devastating injuries from severe burn or trauma The initial management of this patient population frequently requires blood transfusions or skin allografts, leading to formation of alloantibodies and a high degree of sensitization Sensitized recipients are at risk for antibody-mediated rejection (AMR) and poor graft outcomes Our group has established a model of AMR in sensitized rats and demonstrated accelerated rejection of the hind-limb allograft The aim of this study is to establish a desensitization protocol using haematopoietic stem cell transplantation (HSCT) to prevent AMR in the setting of VCA. Methods Sensitization was established by performing skin transplants from Dark Agouti (DA) donors to Lewis rat recipients Sensitized controls received skin transplant only, whereas the experimental group underwent a desensitization protocol including a 7-day course of fludarabine, myeloablative total body irradiation (12Gy) and syngeneic HSCT Serum donor specific antibody (DSA) levels of both groups were measured using flow cytometry after skin transplant and again after desensitization Orthotopic hind-limb transplantation from DA donors was then performed, and daily tacrolimus (05 mg/kg) was administered thereafter Graft rejection was defined as grade 3 rejection and was assessed by clinical monitoring and histology Complement deposition was examined by performing immunohistochemistry for C4d.","PeriodicalId":372758,"journal":{"name":"Vascularized Composite Allotransplantation","volume":"13 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":"115421255","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}
A. Quan, Joseph Lopez, J. Budihardjo, S. Mermulla, T. Jawadi, Howard D. Wang, A. Hoke, S. Tuffaha, W. Lee, G. Brandacher
{"title":"2553: Measuring functional recovery after chronic denervation of peripheral nerves: A novel rat forelimb model","authors":"A. Quan, Joseph Lopez, J. Budihardjo, S. Mermulla, T. Jawadi, Howard D. Wang, A. Hoke, S. Tuffaha, W. Lee, G. Brandacher","doi":"10.1080/23723505.2016.1234233","DOIUrl":"https://doi.org/10.1080/23723505.2016.1234233","url":null,"abstract":"2553: Measuring functional recovery after chronic denervation of peripheral nerves: A novel rat forelimb model Amy Quan, Joseph Lopez, Joshua Budihardjo, Sara Mermulla, Tariq Jawadi, Howard Wang, Ahmet Hoke, Sami Tuffaha, W. P. Andrew Lee, and Gerald Brandacher Johns Hopkins University School of Medicine, Vascularized Composite Allotransplantation (VCA) Laboratory, Baltimore, MD, USA Background Functional outcomes after vascularized composite allotransplantation (VCA) depend on nerve regeneration. After transplantation, the recipient peripheral nerve axons slowly grow and reinnervate the graft. Meanwhile, the target composite tissues (i.e., muscle, nerves) are chronically denervated, causing significant damage to axons, Schwann cells, and muscle, which leads to decreased nerve regeneration potential. There are currently no studies that reliably measure the effects of chronic denervation (CD) on graft function. Thus, we have developed a novel nerve injury rat model that optimizes the measurement of functional recovery after CD. Methods In our forelimb chronic denervation model, the median nerve was transected at the mid-humerus level and left in discontinuity for 0, 8, or 12 weeks. After the period of CD, the distal median nerve stump was coapted to the proximal end of a freshly axotomized ulnar nerve. Group 1 rats underwent 8 weeks of CD (n D 8); Group 2 underwent 12 weeks of CD (n D 8); Group 3 (positive control) did not undergo CD but instead underwent immediate ulnar-median neurorrhaphy (n D 8); and Group 4 (naive control) did not undergo any surgery (nD 8). Functional recovery was monitored weekly by measuring grip strength, feeding ability, and compound muscle action potentials (CMAPs) in median nerve-innervated muscles. Animals were sacrificed at 14 weeks after ulnar-median neurorrhaphy for assessment of axonal regeneration and degree of muscle atrophy.","PeriodicalId":372758,"journal":{"name":"Vascularized Composite Allotransplantation","volume":"227 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":"123466751","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}
G. Furtmuller, B. Oh, Madeline L. Fryer, J. Dodd-o, S. Ganguly, G. Raimondi, D. Cooney, W. Lee, L. Luznik, G. Brandacher
{"title":"2587: Vascularized composite allotransplantation combined with donor bone marrow and post transplantation high-dose cyclophosphamide (PTCy) induces immune tolerance after reconstructive transplantation","authors":"G. Furtmuller, B. Oh, Madeline L. Fryer, J. Dodd-o, S. Ganguly, G. Raimondi, D. Cooney, W. Lee, L. Luznik, G. Brandacher","doi":"10.1080/23723505.2016.1233036","DOIUrl":"https://doi.org/10.1080/23723505.2016.1233036","url":null,"abstract":"2587: Vascularized composite allotransplantation combined with donor bone marrow and post transplantation high-dose cyclophosphamide (PTCy) induces immune tolerance after reconstructive transplantation Georg J. Furtmuller, MD, Byoung Chol Oh, DVM, PhD, Madeline Fryer, BS, Jeffrey Dodd-o, MD, PhD, Sudipto Ganguly, PhD, Giorgio Raimondi, PhD, Damon Cooney, MD, PhD, W. P. Andrew Lee, MD, Leo Luznik, MD, and Gerald Brandacher, MD Johns Hopkins University School of Medicine, Vascularized Composite Allotransplantation (VCA) Laboratory, Baltimore, MD, USA; Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA Background Reconstructive transplantation has become an enthusiastically employed means for reconstruction of devastating tissue defects However, conventional immunosuppression required to maintain allograft survival hinders its widespread application The treatment concept presented here is designed to induce immunosuppression-free allograft survival Methods: Murine skin, heart, and hindlimb transplants were performed across a full MHC mismatch barrier Recipients were treated with PTCy (ie non-myeloablative TBI, T-cell depletion and a single dose of post-transplant cyclophosphamide) with and without donor BM and splenocytes (DBM) Mixedand regulatory T cell chimerism as well as Vb-TCRstaining was performed Donor-specific unresponsiveness was tested via mixed lymphocyte reactions (MLR) and by secondary skin and heart transplant challenge. Results Untreated animals rejected allogeneic skin grafts, hearts and hindlimbs acutely within 14 § 1 days, 9 §2 days, and 8 § 1 days, respectively The PTCy extended skin and heart graft survival (32 § 8; 65 § 4 days, respectively) Additional DBM augmentation lead to allograft survival of >150 days in skin and heart Indefinite graft survival of >250 days was observed in all animals receiving the induction regimen and a VCA § DBM In groups receiving a VCA with and without DBM, donor chimerism was detected at 3017% § 872% and 2251% § 596%, respectively Regulatory T cell chimerism showed recipient-derived Tregs predominantly contributing to the Treg pool (926C/¡ 42%) in the early phase after transplantation (POD 14–30) whereas at later time points (POD 60-100) donor-derived Foxp3C cells contributed equally (462 C/¡ 113%). Gradual depletion of developing T cell clones by donor-derived cells, shown by progressive reduction in circulating Vb5/11C T cells, indicates actuation of central mechanism for tolerance induction All long-term survivors showed donor-specific T cell unresponsiveness invitro (MLR) while demonstrated proliferation against 3rd party stimulators In-vivo, tolerant animals rejected 3rd party skin while donor-matched tissues were accepted long-term (skin and heart). Conclusion Robust tolerance and immunosuppression-free long-term allograft survival can be induced combining DBM transplantation with PTCy in a fully MHC-mismatched murine models of skin, heart, and VCA The intragraft vascul","PeriodicalId":372758,"journal":{"name":"Vascularized Composite Allotransplantation","volume":"35 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":"125385887","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}
M. Suchyta, M. Sabbagh, M. Morsy, S. Mardini, S. Moran
{"title":"Advances in peripheral nerve regeneration as it relates to VCA","authors":"M. Suchyta, M. Sabbagh, M. Morsy, S. Mardini, S. Moran","doi":"10.1080/23723505.2017.1344347","DOIUrl":"https://doi.org/10.1080/23723505.2017.1344347","url":null,"abstract":"ABSTRACT Vascularized composite allotransplant (VCA) offers functional, social, and quality of life improvements for patients who have exhausted traditional reconstructive options. Unlike solid organ transplant, VCA success is not only based upon the quality of perfusion and level of immunosuppression, but also on the success of nerve regeneration within the transplanted part. This paper will summarize the present state of peripheral nerve regeneration in the context of VCA and will explore the latest research advances that will affect the future of the field. These advances offer promising future strategies to improve patient outcomes in VCA.","PeriodicalId":372758,"journal":{"name":"Vascularized Composite Allotransplantation","volume":"14 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":"128872004","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}