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Protecting Donor Livers During Normothermic Machine Perfusion With Stem Cell Extracellular Vesicles.

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Two rapidly growing areas in transplantation research are the use of normothermic machine perfusion (NMP) of donor organs and the therapeutic use of stem cell-derived extracellular vesicles (EVs) to improve… Click to show full abstract

Two rapidly growing areas in transplantation research are the use of normothermic machine perfusion (NMP) of donor organs and the therapeutic use of stem cell-derived extracellular vesicles (EVs) to improve graft viability. In this issue of Transplantation, Rigo et al describe the first study to combine these two exciting fields in an innovative approach to recondition injured donor livers before transplantation. The utilization of extended criteria donor (ECD) livers is increasing in an attempt to keep up with the growing gap between liver supply and demand. Thus, to improve outcomes of transplanted ECD livers, graft optimization or repair strategies are being evaluated.One such strategy is the application of NMP to better preserve donor livers as well as to recondition ECD livers. Unlike cold storage (CS) or hypothermicmachine perfusion, NMP restores physiological conditions by continuously supplying oxygen and nutrients at normothermic (37°C) temperature during ex situ liver preservation. The goal here is to minimize (or avoid) ischemia and hypothermia and provide a means to assess organ viability before transplantation. For example, Karangwa et al recently demonstrated that elevated D-dimer (a marker of fibrinolysis) concentration during liver NMP correlated with ischemiareperfusion injury and may serve as a predictor of poor graft function. Preclinical experiments indicate numerous benefits of NMP over CS, and initial clinical trials demonstrate safety and feasibility. Future studies will determine if NMP might someday replace CS, but the real excitement lies with the use of NMP as a platform for reconditioning ECD livers to expand the donor organ pool. Use of NMP not only enables assessment of organ viability but also provides a novel platform upon which marginal donor organs could be therapeutically reconditioned for

Keywords: extracellular vesicles; perfusion; donor livers; normothermic machine; stem cell; machine perfusion

Journal Title: Transplantation
Year Published: 2018

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