Xiaoxi Wei, PhD, is a co-founder and the CEO of X-Therma. An award-winning entrepreneur and chemist, Dr. Wei is the lead author of eight peer-reviewed research papers and has been awarded six patents. She has served as healthcare advisor—University of California Regents Working Group on Innovation Transfer and Entrepreneurship, as vice chair of the Younger Chemists Committee of the American Chemical Society, and as scientific advisor to the Life Extension Foundation.
The preservation of living cells and tissues is an often-underappreciated obstacle in the clinical lab. Cryogenic temperatures attempt to address this challenge by minimizing biochemical activity within samples of interest. As the cell and gene therapy market grows, the drawbacks of cryopreservation are becoming more apparent.
This article examines the current cryopreservation landscape within the cell and gene therapy market and explores emerging solutions to meeting supply demands and patient safety standards.
Current cryopreservation solutions and limitations
Cryopreservation is essential to banking cells and tissues to facilitate off-the-shelf regenerative medicine. While cryopreservation is the most effective solution for specimen storage, it has significant drawbacks, limiting medical progress.
Typically, cells undergo slow freezing in the presence of a cryoprotectant chemical such as dimethyl sulfoxide (DMSO) or ethylene glycol. Although these chemicals are necessary to prevent ice crystals from forming—the primary driver of cell damage—they can also have detrimental effects and be toxic to both the cells being preserved and the patients receiving cell therapies. Consequently, the concentration of cryoprotectants must be limited.
Vitrification is another cryopreservation method that involves rapid freezing and a high concentration of cryoprotectant. In this case, a combination of chemicals at lower concentrations may reduce their individual toxicities.
However, the shortcomings of both cryopreservation methods highlight the urgent need for a cryoprotectant that prevents the formation of ice crystals without a toxic effect.
What’s ahead in cryopreservation?
Inspired by nature, a new type of cryoprotectant has emerged as a safer alternative to traditional chemicals (such as DMSO) that are used to avoid ice crystal formation. Specifically, arctic fish that can survive in subfreezing conditions inspired research of a novel antifreeze biomimetic known as a peptoid, which extends the shelf life of living medicines, all while minimizing toxicity.
Using peptoids in cryopreservation provides extreme cooling stability due to their superior ability to prevent ice crystal formation. Additionally, peptoids can be easily manufactured, scaled, and integrated into existing cold storage manufacturing processes. As such, the application of this technology does not require special equipment and will make off-the-shelf treatments, such as allogeneic stem cells or CAR-T cells, a standard approach in medicine.
Biopharmaceutical companies are already testing this cryoprotectant through early adoption programs. For example, pluripotent stem cell-derived cardiomyocytes can be processed, packaged, and immediately used in the lab, as there is no true “unfreezing” process that needs to take place.
With such complex, yet potentially curative therapies on the horizon, the need for a more innovative, sophisticated, and safe preservation process is paramount. The cryopreservation field is seeing exciting progress that will strengthen several areas of medicine.