Discover 5 benefits of methylcellulose for cell culture performance
Introduction:
The cell culture landscape is experiencing rapid growth, as culture media is a critical tool for biotech advancements, particularly in the development of biopharmaceuticals. The market is projected to be valued at US$3,513.8 billion in 2024 – and it is set to flourish; estimated to grow at a compound annual growth rate (CAGR) of approximately 7% from 2024 to 2034.i This is, in part, fueled by the increasing adoption of cell cultures for the production of viral vaccines and protein-based therapeutics as well as the rising global demand for advanced therapy medicinal products.1 At the same time, cell culture media are undergoing a transformation, evolving from traditional bovine-derived component systems towards chemically defined and animal derivative-free media. This shift is motivated by the need for improved safety, consistency, and compliance with ethical and regulatory standards – especially given the batch-to-batch variation found with bovine media.ii
To support these modern media, additives are required to help nourish and protect cells during culture processes. One particular compound is being revisited to help advance the ‘new age’ of cell cultures – methylcellulose, a natural polymer derived from cellulose. With more than 30 years of use in cell cultures and across the wider pharmaceutical landscape as an excipient and solution for drug delivery systems, methylcellulose could be the key to cell culture success.iii So, what are the benefits of using methylcellulose in cell culture media? Here, we highlight five key advantages that methylcellulose has to offer.
1. Proven track record
Methylcellulose boasts a well-established history in both cell culture and broader pharmaceutical applications, making it a dependable option for emerging cell culture technologies. Initially, used as a gel-forming agent and stabilizer in various pharmaceutical formulations, its ability to form a gel-like matrix propelled the adoption of methylcellulose in cell lines for growth and differentiation. Since then, the unique properties of methylcellulose have been leveraged in many pharmaceutical applications, including in drug delivery systems and as a pharmaceutical excipient in tablets and capsules, where it functions as a binder and stabilizer. That said, the polymer’s proven performance and adaptability continue to make it an exceptional choice as a cell media additive within the field of biopharmaceutical research and development.
2. Minimize filter clogging with a new low-fiber solution
Traditional methylcellulose additives can block filter pores which slows filtration, reduces flow rates, and increases maintenance needs. In obstructing filters and creating resistance to fluid flow, these materials also complicate sterilization processes, necessitating more frequent cleaning or even replacement of filters, and challenges in maintaining consistent and efficient operations, all of which lead to an increased cost for biopharmaceutical manufacturers.iv
The key to resolving filtration issues associated with methylcellulose is using a low-fiber polymer – like METHONOVA™. Joshua Katz, Senior Research and Development Manager at NovaMatrix® and IFF Pharma Solutions, explains how METHONOVA™ can help overcome filtration drawbacks. “METHONOVA™is our advanced, cell-compatible methylcellulose with reduced fiber content. Our internal filtration tests, using two different filter pore sizes, clearly show that METHONOVA™ outperforms traditional methylcellulose polymers of the same viscosity and concentration. Given this, METHONOVA™ enhances production efficiency and extends filter lifespan, as it has a significantly shorter filtration time and no filter clogging. Moreover, it is easy to sterilize, being both autoclavable and filterable, making it a standout methylcellulose solution compared to other materials on the market.”
3. Improve cell culture process efficiencies
Methylcellulose is an optimal choice as an additive in cell cultures for several reasons. It is long-known to be an effective shear protectant for cells cultured in suspension.v Here, it shields cells from mechanical stress and agitation in bioreactors, thus helping to maintain cell viability and reducing cell aggregation. Additionally, methylcellulose supports nutrient availability, promoting optimal cell growth and productivity, and facilitates a seamless scale-up from small to large-scale cultures. It can also help to form a 3D gel matrix that mimics in vivo conditions, which promotes better cell attachment, growth, and proliferation for adherent cell cultures.
Louis Ruocco, global strategic marketing director, IFF Pharma Solutions shared his insights on how METHONOVA™ methylcellulose, the latest addition to our NovaMatrix® range of biopolymers, can be used to increase cell line productivity of Chinese hamster ovary (CHO) cells specifically. “CHO cells are one of the most common cell lines used in the biotechnology market – utilized for the production of therapeutic proteins, monoclonal antibodies and other biopharmaceuticals.In CHO cell production, methylcellulose can be used as a low-viscosity additive that provides shear protection without significantly raising the media viscosity. This is important because changes to media viscosity can directly affect cellular responses, including nutrient uptake, cell growth and protein production. Methylcellulose, therefore, makes it possible to protect cells from shear stress while maintaining an environment that supports optimal cell performance.vi
“Our latest trials exploring the use of our methylcellulose, METHONOVA™, in a model suspension CHO cell line in xeno-free media showed a 50% improvement in viable cell density compared to Poloxamer 188, another commonly used polymer in cell culture media.vii In addition, there was a 30% boost in antibody production over a 14-day culture. Equally important, there were no changes in protein quality. These findings demonstrate that you can easily achieve process intensification and significantly improve cell culture productivity with METHONOVA™.”
4. Methylcellulose: a cool addition in cryopreservation
Cryopreservation involves cooling biological samples to temperatures well below freezingviii to halt all metabolic and biochemical processes, thereby preserving them for extended periods. Cryopreservation has multiple important applications but is highly attractive as a means to preserve organs and bank large quantities of tissues and cells for the discovery, development, and production of drugs.ix However, it does come with drawbacks – namely maintaining a sufficient number of viable cells ready for use.
Typically, dimethyl sulfoxide (DMSO) and fetal bovine serum are used to protect cells during freezing, but these can pose risks such as toxicity and cell death with DMSO and variability, as well as ethical and regulatory concerns listed above for bovine serums.x In response to these issues, researchers are exploring alternative cryoprotectants and serum-free formulations to reduce toxicity and improve safety in human cell therapies and other medical applications.
Studies have demonstrated the promise of methylcellulose as a cryoprotective agent in serum-free cultures, where it safeguards cells during the freeze-thaw cycle and improves recovery post-thaw. One specific paper found that methylcellulose combined with other agents, like Poloxamer 188, helped to reduce DMSO levels (at least up to 50%) and enabled the removal of serum without compromising cell viability or denaturing the cells.xi This confirms that methylcellulose can be added to cryopreservation applications to enhance cell recovery after thawing.
5. Enable chemically defined media to thrive
Methylcellulose supports the transition from bovine-based media to chemically defined and animal-free systems. Developing and optimizing cell culture media requires a mixture of nutrients, such as supplements and growth factors, that help cells grow.xii Historically, cell cultures have relied on animal-derived products such as fetal bovine serum. However, concerns related to the safety and ethical implications of using animal-origin components in this field have influenced the uptake of chemically defined and animal-free media by the pharmaceutical industry. Furthermore, bovine serums are difficult to fully characterize, prone to inconsistency, and subject to batch-to-batch variation. These issues can result in limited reproducibility and unreliable experimental outcomes, complicating research efforts and reducing accuracy of findings. On the other hand, cell culture media that are free from animal-derived components and contain well-defined ingredients minimize the risk of unintended experimental effects, thereby improving the reliability and reproducibility of the generated product.
Methylcellulose plays a valuable role in the transition from bovine to chemically defined and non-animal media because it can (at least partially) substitute the bovine serum used in traditional cell culture media to help grow various cell lines. By offering a consistent and controlled environment for cell growth, methylcellulose could be pivotal for achieving reliable and reproducible research outcomes in modern media.
Harness the power of METHONOVA™ methylcellulose
Our experts leverage decades of polymer science expertise to enable innovations that will help you succeed – including METHONOVA™, a cutting-edge methylcellulose solution ideal for biotech and biopharmaceutical applications such as advanced cell culture media. If you would like to learn more about the benefits that METHONOVA™ can bring to your cell culture processes or other applications, visit: METHONOVA™ Products - Pharma Solutions (iff.com)
Do you have a specific question regarding METHONOVA™? Talk to one of our experts today.
