Mesenchymal Stromal Cells as Anti-Inflammatory and Regenerative Mediators for Donor Kidneys During Normothermic Machine Perfusion

Sierra-Parraga, Jesus Maria; Eijken, Marco; Hunter, James; Moers, Cyril; Leuvenink, Henri G. D.; Møller, Bjarne Kuno; Ploeg, Rutger J.; Baan, Carla C.; Jespersen, Bente; Hoogduijn, Martin J.

doi:10.1089/scd.2017.0030

Cited by 37 publications

(30 citation statements)

References 106 publications

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“…First, the combination of machine perfusion and additional agents including antibodies or alternative therapeutics (48, 49) may provide a synergistic effect with regard to organ preservation and reduction of IRI. Second, consideration of the influence of age is strongly recommended for upcoming clinical trials.…”

Section: Discussionmentioning

confidence: 99%

Graft Pre-conditioning by Peri-Operative Perfusion of Kidney Allografts With Rabbit Anti-human T-lymphocyte Globulin Results in Improved Kidney Graft Function in the Early Post-transplantation Period—a Prospective, Randomized Placebo-Controlled Trial

et al. 2018

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Introduction: Although prone to a higher degree of ischemia reperfusion injury (IRI), the use of extended criteria donor (ECD) organs has become reality in transplantation. We therefore postulated that peri-operative perfusion of renal transplants with anti-human T-lymphocyte globulin (ATLG) ameliorates IRI and results in improved graft function.Methods: We performed a randomized, single-blinded, placebo-controlled trial involving 50 kidneys (KTx). Prior to implantation organs were perfused and incubated with ATLG (AP) (n = 24 kidney). Control organs (CP) were perfused with saline only (n = 26 kidney). Primary endpoint was defined as graft function reflected by serum creatinine at day 7 post transplantation (post-tx).Results: AP-KTx recipients illustrated significantly better graft function at day 7 post-tx as reflected by lower creatinine levels, whereas no treatment effect was observed after 12 months surveillance. During the early hospitalization phase, 16 of the 26 CP-KTx patients required dialysis during the first 7 days post-tx, whereas only 10 of the 24 AP-KTx patients underwent dialysis. No treatment-specific differences were detected for various lymphocytes subsets in the peripheral blood of patients. Additionally, mRNA analysis of 0-h biopsies post incubation with ATLG revealed no changes of intragraft inflammatory expression patterns between AP and CP organs.Conclusion: We here present the first clinical study on peri-operative organ perfusion with ATLG illustrating improved graft function in the early period post kidney transplantation.Clinical Trial Registration: www.ClinicalTrials.gov, NCT03377283

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Section: Discussionmentioning

confidence: 99%

Graft Pre-conditioning by Peri-Operative Perfusion of Kidney Allografts With Rabbit Anti-human T-lymphocyte Globulin Results in Improved Kidney Graft Function in the Early Post-transplantation Period—a Prospective, Randomized Placebo-Controlled Trial

et al. 2018

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“…These cells possess potent regenerative properties mediated through the release of paracrine factors. Several preclinical studies are currently under way to investigate the effect of mesenchymal stem cells (MSC) and stem cell‐derived extracellular vesicles in the setting of kidney and liver MP with promising preliminary results . Gregorini et al .…”

Section: Advances In Organ and Tissue Preservationmentioning

confidence: 97%

“…Treated‐rat kidney grafts displayed significantly less global ischemic damage as well as an up‐regulation of genes encoding enzymes for improved cell energy metabolism and membrane transport. Along with in the murine setting, scientists are currently investigating the potential of MSC therapy in the setting of normothermic ex vivo perfusion in pig kidneys .…”

Section: Advances In Organ and Tissue Preservationmentioning

confidence: 99%

Emerging technologies in organ preservation, tissue engineering and regenerative medicine: a blessing or curse for transplantation?

et al. 2019

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Summary Since the beginning of transplant medicine in the 1950s, 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 the 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 sub‐disciplines and highlights recent advances and existing limitations for widespread clinical application and potential impact on the future of transplantation.

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“…Various preclinical advancements of the NMP technique have been recently suggested, such as the application of therapeutic agents via the perfusion fluid. Examples include the supplementation of mesenchymal stromal cells for immunomodulation or taurocholate to support biliary excretory function . Furthermore, a recent report proposed the utilization of an acellular oxygen carrier instead of packed red blood cells for normothermic MP.…”

Section: Machine Perfusion–basic Principles and Mechanismsmentioning

confidence: 99%

“…64 The first large multicentre randomized clinical trial comparing NMP with SCS for OLT completed recruitment in 2016 ( Table 3). Further, currently ongoing clinical studies to NMP are listed in 66 or taurocholate to support biliary excretory function. 67 Furthermore, a recent report proposed the utilization of an acellular oxygen carrier 68 instead of packed red blood cells for normothermic MP.…”

Section: Cost-outcome Effectivenessmentioning

confidence: 99%

Machine perfusion for liver transplantation in the era of marginal organs—New kids on the block

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Tolba

et al. 2018

Liver International

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In the face of a critical organ shortage in the Western world, various strategies are employed to expand the donor pool for orthotopic liver transplantation (OLT). Among them is the transplantation of organs from extended criteria donors, a valuable source of liver allografts, however, characterized by potential risks for post-OLT complications and inferior outcomes. In recent years, machine perfusion (MP) of the explanted donor liver as well as regional perfusion techniques has witnessed significant advancements. Here, we aim to discuss different modes of dynamic organ preservation in OLT. These include hypothermic and normothermic MP, hypothermic oxygenated machine perfusion (HOPE), controlled oxygenated rewarming as well as regional perfusion protocols. Over recent years, multiple feasibility trials have demonstrated the clinical prospects of MP. In the context of OLT using organs from extended criteria donors, MP has numerous advantages compared to conventional cold storage, some of which include the preservation and reconditioning of borderline transplantable organs and the viability assessment of high-risk donor allografts. This review aims to address the topic of liver allograft MP, highlighting particularly the current trends in clinical applications and future perspectives. Furthermore, different approaches of liver storage and reconditioning are reviewed in the context of ongoing research.

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Mesenchymal Stromal Cells as Anti-Inflammatory and Regenerative Mediators for Donor Kidneys During Normothermic Machine Perfusion

Cited by 37 publications

References 106 publications

Graft Pre-conditioning by Peri-Operative Perfusion of Kidney Allografts With Rabbit Anti-human T-lymphocyte Globulin Results in Improved Kidney Graft Function in the Early Post-transplantation Period—a Prospective, Randomized Placebo-Controlled Trial

Graft Pre-conditioning by Peri-Operative Perfusion of Kidney Allografts With Rabbit Anti-human T-lymphocyte Globulin Results in Improved Kidney Graft Function in the Early Post-transplantation Period—a Prospective, Randomized Placebo-Controlled Trial

Emerging technologies in organ preservation, tissue engineering and regenerative medicine: a blessing or curse for transplantation?

Machine perfusion for liver transplantation in the era of marginal organs—New kids on the block

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