Abstract
A three-dimensional multicellular organism maintains the biological functions of life support by using the blood circulation to transport oxygen and nutrients and to regulate body temperature for intracellular enzymatic reactions. Donor organ transplantation using low-temperature storage is used as the fundamental treatment for dysfunctional organs. However, this approach has a serious problem in that donor organs maintain healthy conditions only during short-term storage. In this study, we developed a novel liver perfusion culture system based on biological metabolism that can maintain physiological functions, including albumin synthesis, bile secretion and urea production. This system also allows for the resurrection of a severely ischaemic liver. This study represents a significant advance for the development of an ex vivo organ perfusion system based on biological metabolism. It can be used not only to address donor organ shortages but also as the basis of future regenerative organ replacement therapy.
Highlights
A three-dimensional multicellular organism maintains the biological functions of life support by using the blood circulation to transport oxygen and nutrients and to regulate body temperature for intracellular enzymatic reactions
We developed a novel liver perfusion culture system based on biological metabolism that can maintain physiological functions, including albumin synthesis, bile secretion and urea production
At temperatures of 4, 10, 22, 33 and 37uC, we evaluated the concentration of alanine aminotransferase (ALT) as a hepatic disorder marker, and we measured albumin and bile as variables representing liver-specific physiological functions
Summary
A three-dimensional multicellular organism maintains the biological functions of life support by using the blood circulation to transport oxygen and nutrients and to regulate body temperature for intracellular enzymatic reactions. We developed a novel liver perfusion culture system based on biological metabolism that can maintain physiological functions, including albumin synthesis, bile secretion and urea production. In a metabolome analysis using cultured hepatocytes, we determined that a biological window for cell survival, but not cell proliferation and function, exists in the hypothermic zone of approximately 22uC, and we found that hypothermic temperature could regulate the biological factors involved in cell survival, such as ATP synthesis, amino acid synthesis and glucose metabolism This 3D perfusion culture based on biological responses was able to preserve a donor liver in vitro and could be used to resuscitate a DCD liver. This study represents a concept that has considerable potential as a novel organ preservation and restoration method for the generation of 3D organ culture
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