Ischemia and reperfusion injury (IRI) in vascularized tissue allotransplantation (VCA) remain largely undefined. Because VCA is comprised of different tissues, the sensitivity towards IRI may not be uniform. We, herein, attempt to address mechanistic aspects of IRI in VCA and provide a summary on potential technologies and targets for amelioration or treatment of IRI in this novel field. IRI results in a loosened architecture of musculature, hypertrophic, centrally located cell nuclei as well as a high degree of neovascularization. Mitochondria in muscle tissue show a high degree of degeneration after prolonged ischemia whereas the ultrastructure remains normal after short cold ischemia time (CIT). Muscle cell necrosis accompanied by a diffuse inflammatory infiltrate and vasculopathy of small vessels is observed after 30 h of CIT. Nerves revealed a high degree of separation and vacuolization of myelin lamellae because of Wallerian degeneration. Approaches to minimize IRI include use of novel preservation solutions, administration of antioxidative and anti-inflammatory molecules/drugs as well as the implementation of machine perfusion in the setting of VCA. Hand and face transplantations are logistically challenging procedures. Optimal planning and a highly congruent and motivated team are key to keep ischemia times to a minimum. In addition to pharmacological approaches, machine perfusion seems promising to help circumvent logistic problems and expand the donor pool in VCA.

The present review discusses current developments in tolerance induction for solid organ transplantation with a particular emphasis on chimerism-based approaches. It explains the basic mechanisms of chimerism-based tolerance and provides an update on ongoing clinical tolerance trials. The concept of “delayed tolerance” is presented, and ongoing preclinical studies in the nonhuman primate setting—including current limitations and hurdles regarding this approach—are illustrated. In addition, a brief overview and update on cell-based tolerogenic clinical trials is provided. In a critical approach, advantages, limitations, and potential implications for the future of these different regimens are discussed.

Background The effect of cold ischemia (CI) in vascularized composite allotransplantation is unknown. We herein assess tissue-specific damage, acceptable CI time, and the effect of preservation solutions in a syngenic rat hindlimb transplant model. Methods Lewis rat limbs were flushed and stored for 2, 10, or 30 hr CI in saline, histidine-tryptophan-ketoglutarate or University of Wisconsin preservation solution before transplantation. Morphologic alterations, inflammation, and damage of the individual tissues were analyzed on day 10 using histomorphology, confocal, light, and transmission-electron microscopy. Results Two-hour CI led to mild inflammation of tissues on day 10, whereas 10-hr and 30-hr CI resulted in massive inflammation and tissue damage. Although muscle was mainly affected after prolonged CI (≥10 hr), nerve was affected in all CI groups. A perineural cell infiltrate, hypercellular appearance, pronounced vacuolization, and mucoid degeneration, appearing as Wallerian degeneration, were observed. Staining with propidium iodide and Syto 16 revealed a decrease in viable muscle cell nuclei in the anterior tibial muscle on day 10 in all groups, which was most pronounced in 10-hr and 30-hr CI animals. Transmission-electron microscopy indicated that a large number of mitochondria were degenerated in the 10-hr and 30-hr CI groups. Histidine-tryptophan-ketoglutarate preservation solution slightly decreased inflammation and tissue damage compared to University of Wisconsin-treated and saline-treated animals, especially in skin and muscle when CI times did not exceed 10 hr. Conclusion Severe inflammation and tissue damage are observed after prolonged CI in muscle and nerve. Ischemia times in vascularized composite allotransplantation should be kept as short as possible and certainly below 10 hr.

It has been hypothesized that transplanting simultaneous pancreas kidney (SPK) grafts from donors with a history of cardiac arrest and cardiopulmonary resuscitation (CACPR) leads to inferior post‐transplant outcomes due to organ hypoperfusion during cardiac arrest and mechanical trauma during resuscitation. Using SRTR data, we identified 13,095 SPK transplants from 2000‐2018, of which 810 (6.2%) were from donors with a history of CACPR. After inverse probability of treatment weighting on donor and recipient characteristics, we found that 1‐, 5‐ and 10‐year patient (CACPR: 96.4%, 89.9% and 78.9%; non‐CACPR: 96.3%, 88.9% and 76.0%; p=0.3), death‐censored pancreas graft survival (CACPR: 89.3%, 82.7%, 75.0%; non‐CACPR: 89.9%, 82.7%, 76.3%; p=0.7), and death‐censored kidney graft survival (CACPR: 97.0%, 89.5%, 78.2%; non‐CACPR: 96.9.9%, 88.7%, 80.0%; p=0.4) were comparable between the two groups. There were no differences in the risk of pancreatitis (CACPR: 2.9%, non‐CACPR: 2.4%; weighted OR=_0.74 1.22 _2.02; p=0.4), anastomotic leak (CACPR: 1.6%, non‐CACPR: 2.0%; weighted OR=_0.54 1.02 _1.93; p>0.9), or median length of hospital stay (CACPR: 8 days, non‐CACPR: 9 days; p=0.6) for recipients of CACPR vs. non‐CACPR donors. Our findings suggest that CACPR donors could be used to expand the SPK donor pool without compromising short or long‐term outcomes.

Since the beginning of transplant medicine in the 1950's, advances in surgical technique and immunosuppressive therapy have created the success story of modern organ transplantation. However, today more than ever, we are facing a huge discrepancy between organ supply and demand, limiting the potential for transplantation to save and improve the lives of millions. To address current limitations and shortcomings, a variety of emerging new technologies focusing on either maximizing the availability of organs or on generating new organs and organ sources hold great potential to eventully overcoming these hurdles. These advances are mainly in the field of regenerative medicine and tissue engineering. This review gives an overview of this emerging field and its multiple subdisciplines and highlights recent advances and existing limitations for widespread clinical application and potential impact on the future of transplantation.

Between 2000 and 2014, five patients received bilateral hand (n=3), bilateral forearm (n=1) and unilateral hand (n=1) transplants at the Innsbruck Medical University Hospital. We provide a comprehensive report of the long‐term results at 20 years. During the 6‐20 years follow‐up, 43 rejection episodes were recorded in total. Of these, 27.9 % were antibody‐related with serum donor‐specific alloantibodies (DSA) and skin‐infiltrating B‐cells. The cell phenotype in rejecting skin biopsies changed and C4d‐staining increased with time post‐transplantation. In the long‐term, a change in hand appearance was observed. The functional outcome was highly depending on the level of amputation. The number and severity of rejections did not correlate with hand function, but negatively impacted on the patients´ well‐being and quality of life. Patient satisfaction significantly correlated with upper limb function. One hand allograft eventually developed severe allograft vasculopathy and was amputated at seven years. The patient later died due to progressive gastric cancer. The other four patients are currently rejection‐free with moderate levels of immunosuppression. Hand transplantation remains a therapeutic option for carefully selected patients. A stable immunologic situation with optimized and individually adopted immunosuppression favors good compliance and patient satisfaction and may prevent development of DSA.