Extracorporeal machine perfusion of the pancreas: technical aspects and its clinical implications – a systematic review of experimental models

Kuan, Kean Guan; Wee, Mau Nam; Chung, Wen Yuan; Kumar, Ramesh; Mees, Soeren Torge; Dennison, Ashley R.; Maddern, Guy J.; Trochsler, Markus

doi:10.1016/j.trre.2015.06.002

Cited by 23 publications

(14 citation statements)

References 78 publications

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“…Ex vivo normothermic machine perfusion (NMP) is a recently developed method of improving organ function prior to transplantation 22 . For many organs (kidneys, pancreas, and lungs), NMP has been used successfully to both preserve and re-condition organs for transplantation 22 – 24 . Here, we simulate NMP by perfusion through a single blood vessel with CIITA siRNA-loaded PACE nanoparticles and show effective and reliable particle uptake and MHC class II molecule silencing in the vascular endothelial cells.…”

Section: Introductionmentioning

confidence: 99%

Ex vivo pretreatment of human vessels with siRNA nanoparticles provides protein silencing in endothelial cells

et al. 2017

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Human endothelial cells are initiators and targets of the rejection response. Pre-operative modification of endothelial cells by small interfering RNA transfection could shape the nature of the host response post-transplantation. Ablation of endothelial cell class II major histocompatibility complex molecules by small interfering RNA targeting of class II transactivator can reduce the capacity of human endothelial cells to recruit and activate alloreactive T cells. Here, we report the development of small interfering RNA-releasing poly(amine-co-ester) nanoparticles, distinguished by their high content of a hydrophobic lactone. We show that a single transfection of small interfering RNA targeting class II transactivator attenuates major histocompatibility complex class II expression on endothelial cells for at least 4 to 6 weeks after transplantation into immunodeficient mouse hosts. Furthermore, silencing of major histocompatibility complex class II reduces allogeneic T-cell responses in vitro and in vivo. These data suggest that poly(amine-co-ester) nanoparticles, potentially administered during ex vivo normothermic machine perfusion of human organs, could be used to modify endothelial cells with a sustained effect after transplantation.

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Section: Introductionmentioning

confidence: 99%

Ex vivo pretreatment of human vessels with siRNA nanoparticles provides protein silencing in endothelial cells

et al. 2017

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“…pre-implantation). Current pancreatic MP work is lacking in the sphere of clinical transplantation, and is limited to pre-clinical animal and discarded human pancreas studies; only the latter will be the focus of this section, with experimental animal work summarized in detail elsewhere [118][119][120].…”

Section: Machine Perfusionmentioning

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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“…Delorme et al in 1964 introduced a method to perfuse human lower limbs in order to secure basic observation of muscular, neuromuscular, and joint function. However, the concept of machine perfusion gained limited popularity in the 1960s as SCS was introduced with significant advantages represented by low cost and ease of use . Consequently, research in the field of machine perfusion experienced a decline and the following 40 years with only a few studies investigating machine perfusion of extremity …”

Section: Introductionmentioning

confidence: 99%

“…However, the concept of machine perfusion gained limited popularity in the 1960s 11 as SCS was introduced with significant advantages represented by low cost and ease of use. 12 Consequently, research in the field of machine perfusion experienced a decline and the following 40 years with only a few studies investigating machine perfusion of extremity. [13][14][15][16] With emergence of hand transplantation over the last two decades and clinical success reported in machine preservation of solid organs, ex vivo perfusion of extremities also witnessed a new wave of research.…”

Section: Introductionmentioning

confidence: 99%