Mathematical optimization of procedures for cryoprotectant equilibration using a toxicity cost function
Mathematical optimization of procedures for cryoprotectant equilibration using a toxicity cost function
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DOI：
10.1016/j.cryobiol.2012.01.001
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发表时间：
2012-06-01
期刊：
影响因子：
2.7
通讯作者：
Higgins, Adam Z.
中科院分区：
文献类型：
--
作者：
Benson, James D.;Kearsley, Anthony J.;Higgins, Adam Z.
冷冻保存几乎普遍依赖于细胞和组织与高浓度的渗透性化学物质（称为冷冻保护剂或CPA）的平衡。尽管它们具有保护性，但CPA会由于细胞体积的变化以及化学毒性而造成损害。在这项研究中，我们使用以前发表的数据来确定毒性成本函数，这是一个代表毒性造成的累积损害的数量。然后，我们使用这个成本函数来定义和数值求解CPA平衡的最优控制问题，使用人类卵母细胞作为具有高度临床相关性的代表性细胞类型。由此产生的毒性最佳的程序预计产生显着低于传统的逐步程序的毒性。特别是，我们的研究结果表明，毒性最小化CPA除了诱导细胞膨胀到其最大耐受体积，然后加载它与CPA，而在溶胀状态。这种违反直觉的结果与传统的逐步策略有很大不同，传统的逐步策略涉及暴露于连续更高的CPA浓度以避免过度收缩。在本研究中确定的程序有可能显着减少由于毒性和值得进一步调查的损害。(C)2012 Elsevier Inc. All rights reserved.
Cryopreservation nearly universally depends on the equilibration of cells and tissues with high concentrations of permeating chemicals known as cryoprotective agents, or CPAs. Despite their protective properties, CPAs can cause damage as a result of osmotically-driven cell volume changes, as well as chemical toxicity. In this study, we have used previously published data to determine a toxicity cost function, a quantity that represents the cumulative damage caused by toxicity. We then used this cost function to define and numerically solve the optimal control problem for CPA equilibration, using human oocytes as representative cell type with high clinical relevance. The resulting toxicity-optimal procedures are predicted to yield significantly less toxicity than conventional stepwise procedures. In particular, our results show that toxicity is minimized during CPA addition by inducing the cell to swell to its maximum tolerable volume and then loading it with CPA while in the swollen state. This counterintuitive result is considerably different from the conventional stepwise strategy, which involves exposure to successively higher CPA concentrations in order to avoid excessive shrinkage. The procedures identified in the present study have the potential to significantly reduce damage due to toxicity and warrant further investigation. (C) 2012 Elsevier Inc. All rights reserved.