Abstract

Maintaining organ viability between donation and transplantation is of critical importance for optimal graft function and survival. To date in pancreas transplantation, static cold storage (SCS) is the most widely practiced method of organ preservation. The first experiments in ex vivo perfusion of the pancreas were performed at the beginning of the 20th century. These perfusions led to organ oedema, hemorrhage, and venous congestion after revascularization. Despite these early hurdles, a number of factors now favor the use of perfusion during preservation: the encouraging results of HMP in kidney transplantation, the development of new perfusion solutions, and the development of organ perfusion machines for the lung, heart, kidneys and liver. This has led to a resurgence of research in machine perfusion for whole organ pancreas preservation. This review highlights the ischemia-reperfusion injuries assessment during ex vivo pancreas perfusion, both for assessment in pre-clinical experimental models as well for future use in the clinic. We evaluated perfusion dynamics, oedema assessment, especially by impedance analysis and MRI, whole organ oxygen consumption, tissue oxygen tension, metabolite concentrations in tissue and perfusate, mitochondrial respiration, cell death, especially by histology, total cell free DNA, caspase activation, and exocrine and endocrine assessment.

Highlights

  • Maintaining organ viability between donation and transplantation is of critical importance for optimal graft function and survival

  • It is well known that the pancreas is highly susceptible to oedema and ischemia-reperfusion injury during both organ retrieval and preservation, which leads to damaging effects on the graft microvasculature [1] as well as dysfunction of both the endocrine and exocrine pancreas [2]

  • We previously reported that endothelial cells on the outskirts of the islets are sensitive to cleaved caspase-3 immunohistochemistry [36]

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Summary

Introduction

Maintaining organ viability between donation and transplantation is of critical importance for optimal graft function and survival. All perfused pancreases demonstrated oedema, hemorrhage, and venous congestion after revascularization Due to these poor results, there was a decline in research on whole pancreas perfusion for transplantation with a subsequent shift in focus towards islet isolation after HMP [11,12,13,14]. Despite these early hurdles, a number of factors favor the use of perfusion during preservation: the encouraging results of HMP in kidney transplantation, the development of new perfusion solutions and the development of organ perfusion machines for the lung, heart, kidneys and liver. We define the elements of pancreas assessment during ex vivo machine perfusion, both for assessment in pre-clinical experimental models as well as for future use in the clinic

Perfusion Dynamics by Non-Invasive Techniques
Hypothermic Ex Vivo Perfusion
Normothermic Ex Vivo Perfusion
Normothermic Regional Perfusion and Flush
Weight
Impedance Analysis
Invasive Techniques Wet-to-Dry Weight
Temperature by Non-Invasive Techniques
Tissue Metabolite Concentrations
Mitochondrial Respiration
Tissue Oxygen Tension
Perfusate Metabolite Concentrations
Ultrastructure
Caspase Activation
Cell Free DNA of Beta Cell Origin
10. MRI and MRS
Findings
11. Discussion
12. Conclusions
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