Choosing your platform for cell culture scale-up: suspension or adherent?

Cell cultures are valuable, and users desire them to grow under the finest conditions possible. So, when it comes to cell culture methods, should they opt for an adherent or a suspension platform? It all depends.

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The choice of vessel is affected by a wide range of biological and operational aspects, including scale, resources, timing, cell type, and how much—or little—culture inspection and parameter control is necessary. Numerous anchorage-dependent cell types enter via adherent platforms such as flasks, although they do not necessarily sustain scaling. Suspension platforms are scalable, but converting cells to suspension can be much more difficult.

It’s not to say that one is particularly better than the other. You have to consider what your goal is, as well as the constraints of your lab and cleanroom space, budget for capital equipment, and anticipated timelines to go from research to clinical trials, and production scale.

Hannah Gitschier, Development Manager, Corning Life Sciences

Each system has advantages and disadvantages, and there are ways to achieve the best of both worlds.

Advantages of adherent cell culture methods

Roller bottles, flasks, and other adherent cell culture vessels have the distinct advantage of being simple to use and capable of providing biologically appropriate surfaces to anchorage-dependent cell types.

Most tissue-derived cells in the body require a surface or extracellular matrix to support growth and normal proliferation. Adherent cell culture platforms provide scalable options with increasing cell growth surface areas for production, and the option to utilize specialty surface chemistries and coatings that mimic a local microenvironment.”

Hannah Gitschier, Development Manager, Corning Life Sciences

Visualization is also available on some adherent platforms. In contrast to bioreactors, a flask or the bottom layers of a stacked vessel are plainly visible under a microscope.

There are certain cell types where morphology is critical to indicating things beyond just cell health. If you have multipotent or pluripotent stem cells that are subject to spontaneous differentiation, being able to see them is a really important way to catch problems early.”

Hannah Gitschier, Development Manager, Corning Life Sciences

These and other benefits make adherent vessels an appropriate pick for several vaccine and cell and gene therapy initiatives that incorporate anchorage-dependent cell types. Adherent cultures also provide the gift of time, which is a key advantage for businesses racing to enter the market.

If there’s steep competition to be the first to market, time could be one of those high-stake factors. If you already have an adherent-based system being utilized for the development and production of other regulatory approved therapies, and you know how to scale quickly, it might be to your benefit to stick with the same proven platforms to get through clinical trials and approvals.”

Hannah Gitschier, Development Manager, Corning Life Sciences

Advantages of cell suspension culture methods

Small-scale vessels such as Erlenmeyer and spinner flasks as well as huge stirred-tank bioreactors are all used in suspension methods. The value for these methods is straightforward: Obtaining yield scale. plenty of it.

Choosing a cell culture method: Cell suspension or adherent cell surface?

Image Credit: Corning Life Sciences

Suspension platforms are a desirable solution for manufacturers seeking operational effectiveness in the laboratory because of their scalability and control.

However, the tradeoff may necessitate more effort up front. Scientists must modify cell types that depend on anchoring for suspension conditions. That requires time and work.

Anchorage-dependent cells might suffer from growth reduction and lower yields during adaptation. And the shear forces and stresses that occur in suspension culture are detrimental to many cell types, but especially anchorage-dependent primary and stem cells.”

Hannah Gitschier, Development Manager, Corning Life Sciences

Direct visualization is also lacking in cell suspension cultures, but users can still assess how things are doing by looking at other signs and the advantages of having online and in-line process controls.

You still have ways of monitoring cell growth, like pH acidification and oxygen and glucose consumption. Those are indirect measurements of culture growth, but you do lose the ability to look at the cells under a microscope.”

Angel Garcia Martin PhD, MBA, Business Development Manager, Corning Life Sciences

Suspension cultures are still able to produce the large amounts of cells required for applications regardless of these difficulties. A typical example is the generation of monoclonal antibodies using Chinese hamster ovary (CHO) cells. Scientists altered these cultures to thrive in a suspension environment, and that is now the primary way they are produced.

However, not every program necessitates such a large scale. Autologous therapies and gene therapies for rare diseases or limited patient populations may be sufficiently produced on a lower scale.

Getting the benefits of both

Employing next-generation technologies that give more cell growth surface area inside smaller, more controllable footprints for adherent cell culture or reduced shear stress for suspension cell culture will enable users to maximize the benefits of either method.

This is the concept behind Corning® HYPERStack® technology, which packs more layers into the same footprint as CellSTACK® cell culture vessels while ensuring gas exchange.

Microcarriers, which use stirred-tank reactors, allow for better surface area to volume ratio scaling as well as pH and gas control. To take things a step further, fixed bed bioreactors and developing technology, like the Corning Ascent® Fixed Bed Reactor system, allow for a higher surface area to volume ratio while also immobilizing cells and decreasing the risk of shear stress.

When you start out, flasks or stacked vessels are a preferred option. Once you start growing, and need to achieve production scale, there’s a huge labor and clean room space cost advantage to going with a fixed-bed bioreactor.”

Angel Garcia Martin PhD, MBA, Business Development Manager, Corning Life Sciences

But, in the end, Gitschier and Garcia Martin agree that the strategy is determined by the needs.

There are certainly different benefits to different technologies, depending on your resources, scale, visualization needs, automation requirements, and whether shear stress can be managed or is detrimental to the culture. It's really about identifying what you want to get out of your platform and working from there.”

Hannah Gitschier, Development Manager, Corning Life Sciences

Users are not expected to make the choice on their own. Field application experts from the equipment vendor or consumable manufacturer can usually assist in determining which option is best to support attaining your end objective.

About Corning Life Sciences

A division of Corning Incorporated, Corning Life Sciences is a leading global manufacturer of cell culture products and solutions that enable academic, biotech and biopharma scientists to harness the power of cells to create life-changing innovations. Corning supports a range of application areas including core cell culture, 3D cell culture, bioprocess, cancer research, primary and stem cell research, drug screening, cell and gene therapy, disease modeling, lab automation and more.

Whether your goal is stem cell expansion or viral vector production, Corning Life Sciences platforms, including HYPERStack® vessels that maximize cell growth area in a small footprint, the high-yield Ascent® Fixed Bed Reactor platform, microcarriers, and closed system solutions can help get you there. Choose from hundreds of vessels, the widest selection of cell culture surfaces, and custom media in a variety of single-use technology configurations. Learn more at www.corning.com/lifesciences.

Last updated: Nov 16, 2022 at 9:46 AM

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