High levels of penetrating cryoprotectants (CPAs) can eliminate ice formation during cryopreservation of cells, tissues, and organs to cryogenic temperatures. But CPAs become increasingly toxic as concentration increases. Many strategies have been attempted to overcome the problem of eliminating ice while minimizing toxicity, such as attempting to optimize cooling and warming rates, or attempting to optimize time of adding individual CPAs during cooling. Because strategies currently used are not adequate, CPA toxicity remains the greatest obstacle to cryopreservation. CPA toxicity stands in the way of cryogenic cryopreservation of human organs, a procedure that has the potential to save many lives. This review attempts to describe what is known about CPA toxicity, theories of CPA toxicity, and strategies to reduce CPA toxicity. Critical analysis and suggestions are also included.
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