Utilization of organs from donors after circulatory death for vascularized pancreas and islet of Langerhans transplantation: recommendations from an expert group

Berney, Thierry; Boffa, Catherine; Augustine, Titus; Badet, Lionel; Koning, Eelco J.P. de; Pratschke, Johann; Socci, C.; Friend, Peter J.

doi:10.1111/tri.12681

Cited by 32 publications

(25 citation statements)

References 44 publications

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“… 43 Despite progressive refinement of the technique, islet transplantation is still limited by the supply of high-quality transplantable organs, and institutions and clinicians are turning to the use of lower quality expanded criteria donor (ECD) organs in an attempt to meet an ever-growing demand to increase the donor pool. 44 Cadaveric organs present a significant challenge to successful long-term graft function when compared to organs recovered form living donors. 45 As we gain better understanding of the mechanisms underlying organ dysfunction in deceased donors, we are discovering new targets for therapies to improve organ quality, and significant attention has been devoted to treatments that may protect tissue injury from oxidative stress.…”

Section: Discussionmentioning

confidence: 99%

Novel Fusion Protein Targeting Mitochondrial DNA Improves Pancreatic Islet Functional Potency and Islet Transplantation Outcomes

et al. 2017

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Long-term graft survival is an ongoing challenge in the field of islet transplantation. With the growing demand for transplantable organs, therapies to improve organ quality and reduce the incidence of graft dysfunction are of paramount importance. We evaluated the protective role of a recombinant DNA repair protein targeted to mitochondria (Exscien I-III), as a therapeutic agent using a rodent model of pancreatic islet transplantation. We first investigated the effect of therapy on isolated rat islets cultured with pro-inflammatory cytokines (interleukin-1 β, interferon γ, and tumor necrosis factor α) for 48 h and documented a significant reduction in apoptosis by flow cytometry, improved viability by immunofluorescence, and conserved functional potency in vitro and in vivo in Exscien I-III-treated islets. We then tested the effect of therapy in systemic inflammation using a rat model of donor brain death (BD) sustained for a 6-h period. Donor rats were allocated to 4 groups: (non-BD + vehicle, non-BD + Exscien I-III, BD + vehicle, and BD + Exscien I-III) and treated with Exscien I-III (4 mg/kg) or vehicle 30 min after BD induction. Sham (non-BD)-operated animals receiving either Exscien I-III or vehicle served as controls. Islets purified from BD + Exscien I-III-treated donors showed a significant increase in glucose-stimulated insulin release in vitro when compared to islets from vehicle-treated counterparts. In addition, donor treatment with Exscien I-III attenuated the effects of BD and significantly improved the functional potency of transplanted islets in vivo. Our data indicate that mitochondrially targeted antioxidant therapy is a novel strategy to protect pancreas and islet quality from the deleterious effects of cytokines in culture and during the inflammatory response associated with donation after BD. The potential for rapid translation into clinical practice makes Exscien I-III an attractive therapeutic option for the management of brain-dead donors or as an additive to islets in culture after isolation setting.

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Section: Discussionmentioning

confidence: 99%

Novel Fusion Protein Targeting Mitochondrial DNA Improves Pancreatic Islet Functional Potency and Islet Transplantation Outcomes

et al. 2017

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“…This allows the pancreas preserved using the TLM to generate adenosine triphosphate during storage, prolonging the preservation time [87]. Strong debate still remains over its benefits, if any, when compared to the use of UW solution during CS [88,89] and a recent publication of guidelines recommended against the use of the TLM for preservation of the pancreas preceding islet isolation [85].…”

Section: Two-layer Methodsmentioning

confidence: 99%

“…Additionally, thrombolytics such as streptokinase or tissue plasminogen activator (tPA) can be added to the in situ perfusion fluid, or alternatively our approach is to directly inject tPA into the aorta before commencement of the cold in situ flush; the aim of this is to achieve a higher quality vascular flush through the clearance of microthrombi [82][83][84]. However no comparative evidence exists for or against the use of thrombolytics in DCD pancreas retrieval, although there is certainly enthusiasm for this approach [83,85].…”

Section: Additive(s) To Perfusatementioning

confidence: 99%

Pancreas Retrieval for Whole Organ and Islet Cell Transplantation

Hawthorne¹,

Hameed²,

Pleass³

2018

Organ Donation and Transplantation - Current Status and Future Challenges

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For more than five decades, we have been refining advances in pancreas whole organ and islet cell transplantation as clinical therapies to treat the ever-increasing number of patients suffering from type-1-diabetes. Research and clinical practice have contributed to making both whole organ and cellular transplantation viable therapeutic options for a broader range of patients. Furthermore, both forms of clinical transplantation results have progressively improved, due to the ongoing refinement of organ donation and its various technical processes, combined with the evolution of immunosuppression and patient care now offering excellent long-term treatment for both type-1-diabetes and concomitant renal failure. This chapter provides an overview on how this has been undertaken and achieved over decades to ultimately provide outstanding outcomes on par with other organ transplantation results. Briefly, we cover the history of pancreas retrieval procedures, the importance of donor selection, the intricate processes of the organ donor operation, preservation of the pancreas, and the ideal ways to best improve outcomes for transplantation. Improving and providing the optimal donor and preservation conditions underpinning the success of subsequent whole pancreas or islet transplantation as a safe, effective, and feasible therapeutic option for an increasing number of patients suffering from type-1-diabetes.

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“…Furthermore, it must be taken into account that little information, if any, is available on the histology of the human pancreas should the gland come from donors after cardiac death (i.e. with permanent cessation of circulatory and respiratory functions) [39,40]. In Europe [41] and in the USA [42] there are around 10,000 deceased organ donors per year and only 10-20% of the available pancreases are used for clinical transplantation.…”

Section: Discussionmentioning

confidence: 99%

Organ donor pancreases for the study of human islet cell histology and pathophysiology: a precious and valuable resource

2018

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Direct in vivo assessment of pancreatic islet-cells for the study of the pathophysiology of diabetes in humans is hampered by anatomical and technological hurdles. To date, most of the information that has been generated is derived from histological studies performed on pancreatic tissue from autopsy, surgery, in vivo biopsy or organ donation. Each approach has its advantages and disadvantages (as summarised in this commentary); however, in this edition of Diabetologia, Kusmartseva et al (https://doi. org/10.1007/s00125-017-4494-x) provide further evidence to support the use of organ donor pancreases for the study of human diabetes. They show that length of terminal hospitalisation of organ donors prior to death does not seem to influence the frequency of inflammatory cells infiltrating the pancreas and the replication of beta cells. These findings are reassuring, demonstrating the reliability of this precious and valuable resource for human islet cells research.

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Utilization of organs from donors after circulatory death for vascularized pancreas and islet of Langerhans transplantation: recommendations from an expert group

Cited by 32 publications

References 44 publications

Novel Fusion Protein Targeting Mitochondrial DNA Improves Pancreatic Islet Functional Potency and Islet Transplantation Outcomes

Novel Fusion Protein Targeting Mitochondrial DNA Improves Pancreatic Islet Functional Potency and Islet Transplantation Outcomes

Pancreas Retrieval for Whole Organ and Islet Cell Transplantation

Organ donor pancreases for the study of human islet cell histology and pathophysiology: a precious and valuable resource

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