Model-Guided Design and Optimization of CPA Perfusion Protocols for Whole Organ Cryopreservation.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 37351756.
- Also identified by DOI 10.1007/s10439-023-03255-5 and PMC identifier 10518287.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
Vitrification could enable long-term organ preservation, but only after loading high-concentration, potentially toxic cryoprotective agents (CPAs) by perfusion. In this paper, we combine a two-compartment Krogh cylinder model with a toxicity cost function to theoretically optimize the loading of CPA (VMP) in rat kidneys as a model system. First, based on kidney perfusion experiments, we systematically derived the parameters for a CPA transport loading model, including the following: V<sub>b</sub> = 86.0% (r<sub>a</sub> = 3.86 μm), L<sub>p</sub> = 1.5 × 10<sup>-14</sup> m<sup>3</sup>/(N·s), ω = 7.0 × 10<sup>-13</sup> mol/(N·s), σ = 0.10. Next, we measured the toxicity cost function model parameters as α = 3.12 and β = 9.39 × 10<sup>-6</sup>. Combining these models, we developed an improved kidney-loading protocol predicted to achieve vitrification while minimizing toxicity. The optimized protocol resulted in shorter exposure (25 min or 18.5% less) than the gold standard kidney-loading protocol for VMP, which had been developed based on decades of empirical practice. After testing both protocols on rat kidneys, we found comparable physical and biological outcomes. While we did not dramatically reduce toxicity, we did reduce the time. As our approach is now validated, it can be used on other organs lacking defined toxicity data to reduce CPA exposure time and provide a rapid path toward developing CPA perfusion protocols for other organs and CPAs.
Medical subject headings
- Cryopreservation
- Vitrification