Vascularized Composite Allotransplantation最新文献

{"title":"2565: Localized immunosuppression in vascular composite allotransplantation using hydrogel drug delivery system","authors":"D. Dzhonova, A. Taddeo, R. Olariu, J. Leckenby, Jean-Christophe Prost, C. Bovet, A. Dhayani, P. Vemula, E. Vögelin, R. Rieben","doi":"10.1080/23723505.2016.1233016","DOIUrl":"https://doi.org/10.1080/23723505.2016.1233016","url":null,"abstract":"2565: Localized immunosuppression in vascular composite allotransplantation using hydrogel drug delivery system Dzhuliya V. Dzhonova, Adriano Taddeo, Radu Olariu, Jonathan Leckenby, Jean-Christophe Prost, Cedric Bovet, Ashish Dhayani, Praveen K. Vemula, Esther V€ ogelin, and Robert Rieben Department of Clinical Research, University of Bern, Bern, Switzerland; Plastic, Reconstructive and Hand Surgery, Bern University Hospital, Bern, Switzerland; University Institute of Clinical Chemistry, Bern University Hospital, Bern, Switzerland; Institute for Stem Cell Biology and Regenerative Medicine (inStem), Bangalore, India Background A major barrier for Vascularized Composite Allotransplants (VCA) to be more frequently advised is the necessity of long-term, systemic immunosuppression, elevating the risks of kidney and liver toxicity, cancer and opportunistic infections in patients To minimize these risks, we developed a hydrogel drug delivery system, which can be injected directly into the graft and locally releases immunosuppressive drugs in response to inflammation We now aimed to demonstrate that this hydrogel indeed responds to inflammation in vivo with drug release and provides adequate immunosuppression in experimental VCA. Methods To show on-demand drug release, hydrogel loaded with tacrolimus was injected in hind-limbs of na€ıve Lewis rats After 7 d rats were challenged with lipopolysaccharide (LPS) sc in the same limb to induce inflammation Tacrolimus blood levels were then monitored To assess long-term graft survival using the hydrogel and study the immunological response in this context, hydrogel loaded with tacrolimus together with infrared-fluorescent dye was injected in Brown Norway hind-limbs transplanted to Lewis recipients Local and systemic release of tacrolimus as well as fluorescent dye were followed and circulating immune cells were characterized. Results We observed initial burst release (over 65 ng/uL) lasting 48 h after injection of the hydrogel, followed by significant decrease and stabilization of tacrolimus to therapeutically relevant systemic levels for over 30 d LPS injection on day 7 led to increased tacrolimus levels, while animals not receiving LPS did not show increase of tacrolimus release Transplanted hind limbs treated with tacrolimus and fluorescent dye loaded hydrogel showed signs of graft rejection around post-operative day 83 Local levels of dye and tacrolimus in the graft were higher and more stable than systemically FACS analyses of circulating graft T lymphocytes showed significantly higher levels of chimerism in animals treated with the hydrogel than in controls with daily tacrolimus treatment. Conclusions We could confirm that our hydrogel releases tacrolimus in response to inflammation Drug and dye release correlated well, allowing a non-invasive monitoring in future studies, in which repeated injections will be used to promote indefinite graft survival furnishing high intragraft and sub-therapeutic systemic ","PeriodicalId":372758,"journal":{"name":"Vascularized Composite Allotransplantation","volume":"43 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":"116547907","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":"2497: Near normothermic ex-situ perfusion extends human limb allograft survival up to 24 hours","authors":"K. Ozer, N. L. Werner, Fares Alghanem, Stephanie L. Rakestraw, Dylan C. Sarver, B. Nicely, R. Pietroski, P. Lange, S. Rudich, C. Mendias, A. Rojas-Peña, J. Magee, R. Bartlett","doi":"10.1080/23723505.2016.1232926","DOIUrl":"https://doi.org/10.1080/23723505.2016.1232926","url":null,"abstract":"2497: Near normothermic ex-situ perfusion extends human limb allograft survival up to 24 hours Kagan Ozer, MD, Nicole Werner, MD, Fares Alghanem, BS, Stephanie L. Rakestraw, BS, Dylan Sarver, BS, Bruce Nicely, RN, MSN, Richard Pietroski, MS, Paul Lange, MD, Steve M. Rudich, MD, PhD, Chris L. Mendias, PhD, Alvaro Rojas-Pena, MD, John C. Magee, MD, and Robert H. Bartlett, MD University of Michigan, Ann Arbor, MI, USA; Gift of Life, Ann Arbor, MI, USA Background Currently vascularized composite allografts (VCA) are cold preserved (4 C) until transplantation. This process is time limited, as the tissue has to be revascularized within 4–6 hours to minimize ischemia reperfusion (IR) injury. Normothermic perfusion was proposed as an alternative method of preservation in solid organ transplantation Method helps to avoid complications associated with cold preservation and maintains tissue viability without inducing IR injury Using this method, previous investigators demonstrated its potential to prolong swine forelimb allograft survival up to 24 hours (4,5) In this study, we aimed to test this system on human forearm allografts Methods Five human forearms were procured from braindead adult donors under tourniquet control. Following elbow disarticulation, the brachial artery was cannulated. The limb was flushed with heparinized saline and connected to a temperature controlled (30–33 C) ex situ perfusion system (Figure) for 24 hours. The perfusate consisted of plasma and red blood cells with a target hemoglobin (Hb) concentration of 4–6 g/dL. Muscle biopsies (flexor carpi radialis) were obtained at 0, 12, and 24 hours Results Average warm ischemia time was 76 minutes Average arterial systolic pressure was 93§2 mmHg, perfusion flow 310 § 20 mL/min (»6–8% of the donor’s estimated cardiac output), and vascular resistance 153 § 16 mmHg/mL/min. Perfusate had an average pH of 743 § 004 , pCO2 32 § 1 mmHg, pO2 317 § 18 mmHg, and Hb 48 § 04 g/dL Electrolytes (sodium, potassium, chloride) remained within a physiologic range Lactate started to increase steadily throughout the experiment; however, neuromuscular electrical stimulation revealed ongoing contraction throughout the experiment H&E staining showed mild fatty infiltration on some myocytes at 24 hours There was minimal change in fiber size, likely due to variation in age and gender between donors Muscle architecture was preserved at the end of 24 hours perfusion Conclusions All limbs remained viable after 24 hours of nearnormothermic ex situ perfusion as evidenced by ongoing neuromuscular stimulation While no assumptions can be drawn about the long-term function of the extremity, this approach could help extend VCA transplantation to a wider geographic area It also has the potential to circumvent complications associated with cold preservation. CONTACT Kagan Ozer, MD kozer@umich.edu © 2016 Kagan Ozer, Nicole Werner, Fares Alghanem, Stephanie L. Rakestraw, Dylan Sarver, Bruce Nicely, Richard Pietroski, Paul Lan","PeriodicalId":372758,"journal":{"name":"Vascularized Composite Allotransplantation","volume":"50 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":"122936286","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":"2551: Acute skin rejection in non-human primate models of face and hand allotransplantation: Before and after tolerance induction","authors":"Z. Ng, M. DeFazio, H. Powell, D. Leonard, Zachary W. Heroux, A. Lellouch, Ilse M. Schol, J. Kurtz, C. Cetrulo","doi":"10.1080/23723505.2016.1232984","DOIUrl":"https://doi.org/10.1080/23723505.2016.1232984","url":null,"abstract":"BackgroundFollowing face or hand transplantation, maintenance immunosuppression is required to prevent VCA loss However, despite such immunosuppression, up to 85% of patients develop at least an ep...","PeriodicalId":372758,"journal":{"name":"Vascularized Composite Allotransplantation","volume":"59 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":"121675231","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":"2590: Growth hormone ameliorates the effects of chronic denervation injury on peripheral nerve regeneration and improves upper extremity murine function","authors":"Joseph Lopez, A. Quan, J. Budihardjo, Kim X. Sinan, Howard D. Wang, Christopher R Cashman, A. Hoke, S. Tuffaha, W. Lee, G. Brandacher","doi":"10.1080/23723505.2016.1234254","DOIUrl":"https://doi.org/10.1080/23723505.2016.1234254","url":null,"abstract":"2590: Growth hormone ameliorates the effects of chronic denervation injury on peripheral nerve regeneration and improves upper extremity murine function Joseph Lopez, Amy Quan, Joshua Budihardjo, Kim Sinan, Howard Wang, Chris Cashman, 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 Introduction It is well understood that peripheral nerve regeneration is pivotal to facilitate graft function after VCA Therefore, exploring therapies that enhance this process can dramatically improve outcomes The purpose of this study was to assess the impact of growth hormone (GH) therapy on preventing the deleterious effects of chronic denervation (CD) injury on peripheral nerve regeneration and resulting extremity function. Methods We utilized a rat CD model to assess the effects of GH therapy on: a) maintaining denervated muscle and SCs, and b) functional recovery in the setting of CD Four groups of Lewis rats were examined: (1) Group 1 animals (negative control, n D 8) underwent 8 weeks of median nerve CD injury followed by repair; (2) Group 2 animals (experimental, n D 8) underwent 8 weeks of median nerve CD followed by repair and treatment with highly purified lyophilized pituitary porcine GH (06 mg/day); (3) Group 3 animals (positive control, n D 8) underwent nerve surgery without median nerve CD injury; (4) Group 4 animals (na€ıve positive control, n D 8) underwent no nerve surgery All groups underwent weekly functional and CMAP testing for 14 weeks post-nerve repair. Results Group 2 rats demonstrated statistically significant greater functional recovery as compared to Group 1 rats (Hand grip: 18 § 03 N vs 10 § 01 N, P D 0001) at the study endpoint At 12 weeks post-median nerve repair, Group 2 rats demonstrated higher median nerve CMAP amplitude (087 § 017 millivolts vs 048 § 01 millivolts; P D 005) and decreased CMAP latency (156 § 01 msec vs 270 § 01 msec; P D 054), suggestive of improved median nerve regeneration as compared to Group 1 rats Lastly, Group 2 animals demonstrated higher expression of SC proliferation and migration markers, c-Jun and erbB-3, and less muscle atrophy (021 § 002 g vs 017 § 001 g; P D 055) when compared to Group 1 at 8 weeks after sciatic nerve CD. Conclusion Systemic GH therapy can maintain chronicallydenervated muscle and Schwann cells and improve extremity function in the setting of CD Therefore, future studies should explore whether GH therapy can augment functional outcomes after VCA. CONTACT Joseph Lopez jlopez37@jhmi.edu © 2016 Joseph Lopez, Amy Quan, Joshua Budihardjo, Kim Sinan, Howard Wang, Chris Cashman, Ahmet Hoke, Sami Tuffaha, 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-Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/), ","PeriodicalId":372758,"journal":{"name":"Vascularized Composite Allotransplantation","volume":"1 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":"128670511","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":"Program – ASRT 5th Biennial Meeting 2016","authors":"","doi":"10.1080/23723505.2016.1236649","DOIUrl":"https://doi.org/10.1080/23723505.2016.1236649","url":null,"abstract":"","PeriodicalId":372758,"journal":{"name":"Vascularized Composite Allotransplantation","volume":"68 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":"121470391","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":"2529: Software based video analysis of functional outcomes of face transplantation","authors":"S. Fischer, Nicolas Krezdorn, Anne Huang, M. Alhefzi, M. Aycart, H. Kiwanuka, Y. Diehm, T. Win, E. Bueno, B. Pomahac","doi":"10.1080/23723505.2016.1232947","DOIUrl":"https://doi.org/10.1080/23723505.2016.1232947","url":null,"abstract":"2529: Software based video analysis of functional outcomes of face transplantation Sebastian Fischer, MD, Nico Krezdorn, Anne Huang, Muayyad Alhefzi, Mario A. Aycart, Harriet Kiwanuka, Yannick Diehm, Thet S. Win, Ericka M. Bueno, and Bohdan Pomahac Brigham and Women’s Hospital, Boston, MA, USA Introduction Outcomes assessment in face transplantation is necessary to provide evidence in support of this livegiving surgery Current methods, however, are imprecise or prone to subjectivity Software-based video analysis allows for fast, objective and retrospective assessment of the functions related to facial movement and expression of emotions Patients and methods We recorded standard electronic videos of each of our 7 face transplant recipients before as well as every 3 to 6 months after transplantation Each video consists of a patient performing a standard sequence of facial movements We retrospectively analyzed all videos using a customized software (Affdex, iMotions, Boston, MA) that automatically tracks and measures the magnitude and direction of facial movements and expressions by recognizing 24 standard reference anatomical points in the face Subsequently, we compared the measurements obtained for a particular patient with those obtained for the same patient at different time points to assess facial motion recovery Results After a mean follow up of 35 years, every patient had showed significant improvements in facial motor function when compared with pre transplant time points Significant improvements were first observed after an average of 6 months after transplantation In 3 patients with partial face transplants, the extent and quality of motor function of the transplanted parts of the face did not show any significant differences compared to the unaffected part 1 y after transplantation Conclusion Software based video analysis provides the first assessment tool capable for objective, precise and reproducible analysis of facial motor and expressive function after face transplantation Of note, this software works with conventional camera and computer equipment, making widespread use possible Standardized lightning conditions and patients’ compliance with performing the facial motor tasks are required to achieve comparable results. CONTACT Bohdan Pomahac bpomahac@partners.org © 2016 Sebastian Fischer, Nico Krezdorn, Anne Huang, Muayyad Alhefzi, Mario A. Aycart, Harriet Kiwanuka, Yannick Diehm, Thet S. Win, Ericka M. Bueno, 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, 19 http://dx.doi.org/10.1080/237235","PeriodicalId":372758,"journal":{"name":"Vascularized Composite Allotransplantation","volume":"82 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":"131686524","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":"2536: Ex vivo hypothermic perfusion of amputated porcine forelimbs promotes reduced molecular damage to skeletal muscle when compared with conventional cold storage","authors":"N. Krezdorn, D. Sakthivel, M. Aycart, Muayyad Alfhefzi, T. Win, H. Kiwanuka, E. Bueno, I. Sinha, B. Pomahac","doi":"10.1080/23723505.2016.1232962","DOIUrl":"https://doi.org/10.1080/23723505.2016.1232962","url":null,"abstract":"2536: Ex vivo hypothermic perfusion of amputated porcine forelimbs promotes reduced molecular damage to skeletal muscle when compared with conventional cold storage Nicco Krezdorn, Dharaniya Sakthivel, Mario A. Aycart, MD, Muayyad Alfhefzi, Thet-Su Win, Harriet Kiwanuka, Ericka Bueno, Indranil Sinha, and Bohdan Pomahac Brigham and Women’s Hospital, Boston, MA, USA Background Limb allotransplantation is largely limited by the allowable ischemia time in limbs Muscle makes up most of the volume of isolated limbs, and its maximum allowable ischemia time is currently in the order of 4–6–h Extracorporeal perfusion devices may support safe extension of the allowable ischemia time for limb tissues The aim of this study was to assess the effect of different storage modalities on gene expression in porcine forelimbs. Methods Porcine forelimbs were amputated and either perfused with oxygenated acellular supplemented perfusion solution (Perfadex ) for 12 h at 10 C (treatment; n D 3) or stored on ice slurry at 4 C (control; n D 2) before replantation Gene expression profiles in muscle tissues from the amputated limb were analyzed after 2 h on ice as well as after 2–h and 12–h perfusion using a hypoxia gene expression qPCR array of 84","PeriodicalId":372758,"journal":{"name":"Vascularized Composite Allotransplantation","volume":"113 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":"124525215","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":"2555: Belatacept in hand transplantation - Effectiveness and pitfalls","authors":"J. Grahammer, B. Zelger, B. Zelger, Annelies Muehlbacher, D. Oefner, S. Schneeberger, A. Weissenbacher","doi":"10.1080/23723505.2016.1233009","DOIUrl":"https://doi.org/10.1080/23723505.2016.1233009","url":null,"abstract":"2555: Belatacept in hand transplantation Effectiveness and pitfalls Johanna Grahammer, MD, Bettina Zelger, MD, Bernhard Zelger, MD, Annelies Muehlbacher, MD, Dietmar Oefner, MD, Stefan Schneeberger, MD, and Annemarie Weissenbacher, MD Dept. of Visceral Transplant and Thoracic Surgery, Innsbruck Medical University, Innsbruck, Austria; Oxford Transplant Center, Oxford, UK Study purpose Belatacept (CTLA4Ig) is an emerging treatment in solid organ transplantation Effects on the development of donor specific antibodies (DSA) as well as its clinical safety in challenging immunological settings have yet to be explored. Methods Three hand transplanted patients have been converted to a Belatacept-based immunosuppressive regimen at 4 months, 6 y and 9 y after unilateral or bilateral hand and forearm transplantation Patients have received 5 mg/kg Belatacept every 2 weeks, the dosing interval was then extended to 4 weeks after 5 applications All 3 patients were kept on their baseline immunosuppressive medication, consisting of a CNI (Patients A, B, C) or mTOR inhibitor (Patients A and B) plus steroids (Patients A and B) and CellCept (Patient B). Results No adverse effects of Belatacept have been noted so far Patient C, who received Belatacept 4 months after transplantation, can successfully be kept on Tacrolimus monotherapy with a low trough level of »4–5 ng/ml This patient has never developed donorspecific antibodies, and displays normal histologic findings Patient A, who had previously developed DSA but was in a stable immunological state at the time of conversion, is now successfully tapered from baseline immunosuppression without evidence of rejection Patient B, who had DSA at the time of conversion, showed an increase of DSA and worsening graft appearance despite stable levels of his baseline immunosuppression, and needed escalation of his immunosuppression. Discussion The addition of Belatacept to an immunosuppressive regimen can be beneficial in hand transplantation However, our patients showed variable results depending on the immunological state at the time of conversion The application of Belatacept as a “œrescue” medication has to be discussed critically. CONTACT Johanna Grahammer, MD johanna.grahammer@tirol-kliniken.at © 2016 Johanna Grahammer, Bettina Zelger, Bernhard Zelger, Annelies Muehlbacher, Dietmar Oefner, Stefan Schneeberger, and Annemarie Weissenbacher. 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, 27 http://dx.doi.org/10.1080/23723505.2016.1233009","PeriodicalId":372758,"journal":{"name":"Vascularized Composite Allotransplantation","volume":"11 1 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":"126041133","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":"2585: The effect of size discrepancy of human nerve allograft derived epineural conduit on the functional outcomes of nerve regeneration in athymic nude rat model","authors":"M. Strojny, R. Gendek, J. Cwykiel, E. Szilagyi, M. Cyran, Wojciech Malewski, H. Karagoz, M. Siemionow","doi":"10.1080/23723505.2016.1234243","DOIUrl":"https://doi.org/10.1080/23723505.2016.1234243","url":null,"abstract":"2585: The effect of size discrepancy of human nerve allograft derived epineural conduit on the functional outcomes of nerve regeneration in athymic nude rat model Marcin Strojny, Rafal Gendek, Joanna Cwykiel, Erzsebet Szilagyi, Malgorzata Cyran, Wojciech Malewski, Husein Karagoz, and Maria Siemionow University of Illinois at Chicago, Chicago, IL, USA Background Nerve autograft is a gold standard in peripheral nerve regeneration However, it is challenged by limited availability, donor site morbidity and scarring Nerve allografts provide an unlimited source of nerve tissue, which can be matched to the recipient’s injured nerve to support nerve recovery This study aimed to assess the effect of human Epineural Sheath Conduit (hESC) adjusted with tissue adhesive or suture on restoration of long nerve defect in an athymic nude rat model. Methods Restoration of 20 mm of nude rat sciatic nerve defect with hESC filled with saline was performed in 5 groups: Group 1: autograft controls (n D 4), Group 2: mismatched size diameter hESC (n D 2), Group 3: hESC with diameter adjusted with tissue adhesive (n D 4), Group 4: hESC with diameter adjusted with nylon 10-0 suture (n D 2), and Group 5: matched diameter hESC (n D 4) Toe-spread and pinprick analyses were performed at 1, 3, 6, 9, 12 weeks Nerve samples for toluidine blue staining and for fluorescent immunostaining for GFAP, NGF, S-100, laminin B, CD3 and CD4 were harvested at 12 weeks post-surgery Muscle denervation atrophy was assessed by Gastrocnemius Muscle Index (GMI). Results Macroscopic evaluation of nerve conduits at 12 weeks showed no tissue adhesion or local signs of inflammation and good vascularization in all groups Additionally, the shape and integrity of the conduit were preserved The best sensory and motor recovery following hESC application was observed in groups with hESC diameter adjusted with tissue adhesive (Group 3) and matched diameter hESC (Group 5), pinprick 175 and 175; toe-spread 05 and 075, respectively hESC without diameter adjustment (Group 2) and hESC adjusted with sutures (Group 4) showed the worst regeneration GMI measurements were the highest for autograft group (Group 1–035) followed by matched diameter hESC (Group 5–032) and hESC adjusted with tissue adhesive (Group 3–0277). Conclusions We confirmed the feasibility of hESC creation and diameter adjustment hESC conduit with adjusted diameter using tissue adhesive showed sensory and motor recovery comparable to hESC conduit with matched diameter to the rat sciatic nerve. Our new hESC conduit provides an alternative option to the autograft nerve gap repair. CONTACT Marcin Strojny mstrojnymd@gmail.com © 2016 Marcin Strojny, Rafal Gendek, Joanna Cwykiel, Erzsebet Szilagyi, Malgorzata Cyran, Wojciech Malewski, Husein Karagoz, 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.o","PeriodicalId":372758,"journal":{"name":"Vascularized Composite Allotransplantation","volume":"79 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":"123489528","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":"2517: Ex-vivo subnormothermic oxygenated machine perfusion of swine forelimbs enables prolonged graft preservation prior to transplantation","authors":"A. Lellouch, N. Karimian, Z. Ng, Safak Mert, Sharon Geerts, K. Uygun, C. Cetrulo","doi":"10.1080/23723505.2016.1234269","DOIUrl":"https://doi.org/10.1080/23723505.2016.1234269","url":null,"abstract":"2517: Ex-vivo subnormothermic oxygenated machine perfusion of swine forelimbs enables prolonged graft preservation prior to transplantation Alexandre Gaston Lellouch, Negin Karimian, Zhi Yang Ng, Safak Mert, Sharon Geerts, Korkut Uygun, and Curtis L. Cetrulo Harvard University, Boston, MA, USA; Massachusetts General Hospital, Boston, MA, USA Background The current gold standard in tissue preservation is static cold storage (SCS) on ice-cold (0–4 C) UW solution. While SCS slows down graft deterioration, it does not have restorative capabilities. We previously developed an ex-vivo perfusion system for subnomothermic oxygenated machine perfusion (SNMP) to resuscitate cadaveric organs. Recovered livers were perfused for 3 hours and transplanted successfully into recipient rats in 5/6 cases; when scaled up to DCD human livers, SNMP demonstrated sustained and enhanced viability of liver grafts. To expand the donor pool in VCA, we investigated the utility of SNMP on preservation time and resuscitation of ischemic limbs in a swine model. Methods 2 porcine forelimbs were procured and flushed with ice-cold UW on the back table through the cannulated axillary artery and veins. Warm ischemia was 45 mins and SCS was 2 hours. Before starting SNMP, the forelimbs were flushed with 1500 mL of cold Lactated Ringers. During SNMP (3 hours), the amputated forelimbs were perfused by a pressure-controlled system through the axillary artery. The perfusion solution consisted of William’s E medium, which was enriched with dexamethasone, insulin and heparin. A venous outflow was prepared for sample collection. Hemodynamics of the limbs was monitored by evaluation of arterial flow and vascular resistance. Perfusion samples were collected at 30 min intervals for biochemical analysis. Lactate clearance was monitored as a marker of muscle injury. Muscle biopsies were collected at 60 min intervals for measurement of ATP production. Results Arterial outflow and vascular resistance remained stable throughout the perfusion, between 270 and 320 mL/min and 0.23 and 0.26 mmHg/mL/min, respectively. Despite the initial increase in lactate levels from 0.2 mmol/L to > 6 mmol/L, this value remained stable during the final hour of perfusion. The increase in ATP production reflects successful resuscitation of the forelimb, increasing from a baseline of 5500 before perfusion to 7500 nmol/g protein during SNMP. Conclusions SNMP has the potential to both actively preserve and enhance overall preservation of forelimbs in a swine model. It may provide the crucial enabling technology for tissue preservation, transport, and eventual transplantation of VCAs. CONTACT Alexandre Gaston Lellouch alellouch@mgh.harvard.edu © 2016 Alexandre Gaston Lellouch, Negin Karimian, Zhi Yang Ng, Safak Mert, Sharon Geerts, Korkut Uygun, and Curtis L. Cetrulo. Published with license by Taylor & Francis. This is an Open Access article distributed under the terms of the Creative Commons Attribution-Non-Commercial Licen","PeriodicalId":372758,"journal":{"name":"Vascularized Composite Allotransplantation","volume":"93 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":"125014498","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}