Ex Vivo Perfusion Using a Mathematical Modeled, Controlled Gas Exchange Self-Contained Bioreactor Can Maintain a Mouse Kidney for Seven Days

Abstract

Regenerative medicine requires better pre-clinical tools in order to increase the efficiency of novel therapies transitioning to the clinic. Current monolayer cell culture methods are suboptimal for effectively testing new therapies and live mouse models are expensive, time consuming and require invasive procedures. Fetal organ culture, organoids, microfluidics and culture of thick sections of adult organs all aim to fill the knowledge gap between monolayer culture and live mouse studies. Here we report on an ex vivo organ perfusion system that can support whole adult mouse organs. Ex vivo perfusion of healthy and diseased mouse organs allows for real-time analysis that provides immediate feedback and accurate data collection throughout the experiment. Having a suitable normothermic ex vivo perfusion system for mouse organs provides a tool that will help contribute to our understanding of kidney physiology and disease and can take advantage of the many mouse models of human disease that already exist. Furthermore, an ex vivo kidney perfusion system can be used for testing novel cell therapies, drug screening, drug validation and for the detection of nephrotoxic substances. Critical to the success of mouse ex vivo organ perfusion is having a suitable bioreactor to maintain the organ. Here we have focused on the mouse kidney and mathematically modeled, built and validated a bioreactor that can maintain a kidney for 7 days. The long duration of the ex vivo perfusion will help to advance studies on kidney disease and can rapidly test for new regenerative medicine therapies compared to whole animal studies.

Ex Vivo Preservation of Ovine Periosteum Using a Perfusion Bioreactor System

“…Both systems employed silicone (internal diameter: 3.0 mm) (Gecko Optical, Perth, WA, Australia) and Tygon tubing (internal diameter: 3.175 mm) (Masterflex, Vernon Hills, IL, USA), respectively. Silicone tubing is known to be oxygen-permeable, but the perfusate oxygenation was predominately achieved by the dissolution of the atmospheric oxygen in the incubator into the perfusate [ 25 ]. Among the six periostea, periosteum 1 and 2 procured from femur were used as initial trials of our perfusion system, and we stopped the perfusion experiments at day 4.…”

From Free Tissue Transfer to Hydrogels: A Brief Review of the Application of the Periosteum in Bone Regeneration

“…These factors have been proven important in previous similar studies in which the researchers attempted to perfuse scaffold constructs seeded with osteogenic cells to study bone biology, proliferation, and gene expression [ 74 , 75 , 76 ]. Meanwhile, maintaining an efficient oxygen supply to the perfused tissue over the course of an experiment is another critical issue [ 77 ].…”

Correction: Won et al. Ex Vivo Perfusion Using a Mathematical Modeled, Controlled Gas Exchange Self-Contained Bioreactor Can Maintain a Mouse Kidney for Seven Days. Cells 2022, 11, 1822

“…In the original publication [1], there was an error in the legend of Figure 2B. The text in the manuscript's Results section is correct, but the figure legend does not match.…”