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Vascular Microphysiological System for Investigating Endothelial Barrier Function During Organ Preservation and
Yongdeok Kim1,2, Ishan Goswami1,2, Elisabeth Gill1
1Department of Bioengineering and California Institute for Quantitative Biosciences (QB3), University of California, Berkeley, CA, 94720, USA.
Small (Weinheim an Der Bergstrasse, Germany)
|February 20, 2025
Summary
Isochoric supercooling (ISC) preservation offers superior endothelial barrier function recovery post-transplant compared to static cold storage (SCS). This novel vascular microphysiological system (MPS) aids in optimizing organ preservation strategies.
Area of Science:
- Biomedical Engineering
- Organ Transplantation
- Vascular Biology
Background:
- Endothelial cell damage during cold preservation and reperfusion impairs the endothelial barrier, leading to edema and transplant failure.
- Current organ preservation methods, like static cold storage (SCS), have limitations in maintaining endothelial barrier integrity.
- Ischemia-reperfusion injury is a critical challenge in organ transplantation, impacting graft viability.
Purpose of the Study:
- To investigate the combined effects of thermal and fluid perturbations on human endothelial barrier function during organ preservation.
- To compare the efficacy of isochoric supercooling (ISC) preservation against static cold storage (SCS) using a vascular microphysiological system (MPS).
- To establish a physiologically relevant in vitro model for studying ischemia-reperfusion injury in the endothelium.
Main Methods:
- Development and utilization of a vascular microphysiological system (MPS) with integrated electrical impedance measurements.
- Comparison of two organ storage methods: isochoric supercooling (ISC) and static cold storage (SCS).
- Real-time monitoring of endothelial barrier function during preservation and reperfusion protocols.
- Genomic analysis to elucidate molecular mechanisms of injury and recovery.
Main Results:
- Isochoric supercooling (ISC) preservation demonstrated superior recovery of endothelial barrier function during reperfusion compared to static cold storage (SCS).
- ISC enabled longer preservation periods with reduced metabolic activity in endothelial cells.
- Electrical impedance measurements provided real-time quantification of barrier function changes.
- Genomic analysis identified molecular pathways involved in injury and recovery under different preservation conditions.
Conclusions:
- The vascular MPS serves as a valuable in vitro model for recapitulating ischemia-reperfusion injury and evaluating organ preservation strategies.
- Isochoric supercooling (ISC) preservation shows significant promise for improving endothelial barrier function and enhancing organ transplant viability.
- This research provides insights into optimizing organ preservation protocols to minimize post-transplant complications.
