Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

The Establishment of Diseased Human Whole Organ Model by Normothermic Machine Perfusion Technique

Version 1 : Received: 10 August 2023 / Approved: 11 August 2023 / Online: 14 August 2023 (09:16:18 CEST)

How to cite: Tang, Y.; Li, J.; Zhang, T.; Chen, H.; Qin, M.; Chen, H.; Huang, J.; Miao, Z.; Cai, R.; Yang, Y.; Kang, J.; Sun, H.; Zhong, R.; Li, J.; Wang, T.; Chen, M.; Ju, W.; Wang, D.; Guo, Z.; Dan, J.; Li, Y.; He, X.; Zhao, Q. The Establishment of Diseased Human Whole Organ Model by Normothermic Machine Perfusion Technique. Preprints 2023, 2023080967. https://doi.org/10.20944/preprints202308.0967.v1 Tang, Y.; Li, J.; Zhang, T.; Chen, H.; Qin, M.; Chen, H.; Huang, J.; Miao, Z.; Cai, R.; Yang, Y.; Kang, J.; Sun, H.; Zhong, R.; Li, J.; Wang, T.; Chen, M.; Ju, W.; Wang, D.; Guo, Z.; Dan, J.; Li, Y.; He, X.; Zhao, Q. The Establishment of Diseased Human Whole Organ Model by Normothermic Machine Perfusion Technique. Preprints 2023, 2023080967. https://doi.org/10.20944/preprints202308.0967.v1

Abstract

The incidence of liver diseases is on the leading rise worldwide, but there is a lack of exact research models mimic liver diseases. Using the normothermic machine perfusion (NMP) platform to study diseased livers recovered from the liver transplantation (LT) recipients seems promising. Therefore, the aim of this study was to establish the first machine perfusion system called Life-XDL to cultivate diseased liver. Four diseased livers recovered from LT recipients within different diagnoses were collected. The diseased livers were connected to the Life-XDL machine perfusion system that circulated Life-XDL perfusate providing oxygen and nutrients. The pressure and flow of the device was recorded and blood gas analysis and laboratory test of perfusate and bile was examined to analyze the function of the diseased livers. Liver tissues after perfusion were collected for histological analysis. Experiments showed that Life-XDL kept the diseased livers at the physiological state with providing stable hemodynamics and suitable partial pressure of oxygen and carbon dioxide. The results of blood gas analysis and laboratory test results demonstrated restoration and maintenance of metabolism and less damage. Moreover, the bile production of case 1, 3 and 4 diseased livers represented its vivid functionality. The pathological characteristics were kept stable before and after NMP. Overall, we successfully establish the Life-XDL machine perfusion system which specially for diseased human whole liver and develop a new diseased human whole organ model in vitro through normothermic machine perfusion that recapitulate the main features of the human liver disease, which showing great promise as disease modeling platforms.

Keywords

normothermic machine perfusion; diseased livers

Subject

Medicine and Pharmacology, Clinical Medicine

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