Cell cultures are extensively used in basic and translational life science research. Common methods for their transport across labs or research facilities can compromise cell viability, affecting research quality and experimental reproducibility. By maintaining cells under optimal laboratory conditions, live cell shipment technology offers a potential solution for better research outcomes.
Cell cultures form the backbone of the modern laboratory and have led to countless breakthroughs in science, from the development of vaccines against measles and mumps to discovering the role of individual genes in health and disease. Many areas in healthcare and medicine such as biopharmaceuticals, drug discovery, regenerative therapies, and personalized medicine rely heavily on their use.
Cell lines and cultures are often shared between collaborating labs, purchased from companies, or transported from one location to another when experiments require specialized facilities. However, the lack of a robust and reliable method for transporting cells is a crucial factor that compromises the integrity, reproducibility, and quality of research projects.
“Cells are sensitive living systems that need to be looked after carefully, especially when researchers want to attribute a change in the cell’s morphology or function to an experimental condition,” said Corné Swart, Executive Director of Business Development and Global Sales at Cellbox Solutions.
“Specialized cell lines like cardiomyocytes or neurons can take a long time to generate, and experiments like mRNA sequencing can cost up to 10,000€. This is why it is important to ensure that cell-based systems are tightly regulated under optimal conditions from the start to the end of experiments.”
Cryopreservation: the good and the bad
The gold standard of cell transportation over long distances is freezing cells in dry ice or liquid nitrogen to suspend their cellular metabolism — a process called cryopreservation. By using extremely low temperatures, cellular degradation is limited and cell viability can be maintained.
However, cryopreservation has several shortcomings, the first being cryoinjury. During freezing, cells are damaged via osmotic stress and the formation of intracellular ice crystals, which can damage cellular structures. Using an antifreeze to reduce ice crystal formation poses toxicity risks and can further lead to abnormal cell behavior. Overall, the loss in cell viability resulting from cryopreservation can range from 20%–70%, depending on cell type.
After reaching their destination, cells are thawed and allowed to recover. Protocols for cryopreservation and subsequent thawing may differ from one lab to another, which can result in experimental data that is hard to reproduce. Moreover, using a standard, non-optimized protocol can give rise to genetic and epigenetic modifications, as each cell type has an optimal freezing and thawing rate.
“Reliable cell quality and viability are key to the success of projects that depend on cell-based tools and they contribute directly to research reproducibility or its absence,” said Robin Sieg, Global Product Manager at Cellbox Solutions.
“Lack of reproducibility and a feasible logistic solution to transport complex treatments — such as 3D tissue constructs — is a serious problem that commonly obstructs research from getting translated into clinical applications for people to experience any benefit from,” added Sieg.
More than €25.8B ($28B) are spent every year in the US on biomedical research that cannot be reproduced or verified. Paired with the increasing demand for cell culture systems that can more effectively reproduce the natural environment, such as co-cultures, engineered cell constructs, or 3D cell cultures, alternatives to cryopreservation are urgently sought.
Shipping cells alive
Instead of subjugating fragile cells to the harsh cryogenic conditions of frozen transport, live cells can be shipped under temperature-controlled conditions in portable CO2 incubators.
“By maintaining the tightly regulated conditions of a laboratory incubator, live cells can be transported in portable incubators under standard incubation conditions so that unnecessary damage to the cells can be avoided,” said Swart. Furthermore, no toxic substances need to be added and the loss from freeze-thaw time is prevented.
Live cell shipment is especially important for sensitive cell lines like induced pluripotent stem cells (iPSCs) and iPSC-derived cells as unwanted changes in metabolism, gene expression, and protein profile can be avoided.
“Growing sensitive and specialized cell lines takes a lot of time, effort, and costly resources to culture in the laboratory but the slightest perturbation from cryopreservation can cause changes in the gene expression pattern or cellular metabolism,” added Sieg.
To meet the needs of different cell types or cultures, Cellbox Solution’s portable incubators allow for parameter optimization, where the temperature and CO2 concentration can be adjusted from 28oC to 38oC and from 0% to 18% CO2.
And the incubators can handle a wide range of activities, from transporting 2D and 3D cultures to conducting specialized bioassays on-site that involve lab-on-a-chip, microfluidics, or cell toxicity tests.
“In experiments using high complexity cell culture models, cryogenic conditions are not compatible with the rigors of research standards. Cellbox provides highly regulated conditions to deliver a product that is ready to use on arrival,” explained Sieg. “This has a significant impact on the research project and its associated costs.”
The road ahead
Cell cultures are instrumental in driving forward our understanding of the systems that underpin life and disease. This is why research that uses cell cultures as experimental model systems need to put in place a robust and reliable method for cell transport that does not undermine overall research quality.
Live cell shipment technology can maintain the robust and tightly regulated laboratory conditions during transport over both long and short distances. New improvements in the technology can also help cater to the specific and diverse needs of researchers.
“With longer run times, cells can stay in their optimal medium in the Cellbox incubator for longer, facilitating long distance transportation,” commented Swart. With the new technology, shipment and storage are possible for up to three days depending on the product type.
“Improving battery management was a key priority for the latest versions of Cellbox products that are to be released soon, which will result in a substantial increase in the run time. In addition, upgrading the software, sensors, and providing a better app, along with 21 CFR Part 11 compliance for cell manufacturing organizations and cell therapy applications, will help customers manage their cell shipments for all their multifaceted needs.”
To learn more about the live cell shipment technology from Cellbox Solutions, please visit their website.
Images via Shutterstock.com. Headshots courtesy of Cellbox Solutions.
Author: Megha Kalra