Cell Suspension Culture or Adherent Surface: Which Is Right for You?

Your cell cultures are precious, and you want them to have the best growing conditions. So, when it's time to choose a cell culture method, should you go with an adherent or a suspension platform?

It depends.

Vessel choice is influenced by a myriad of operational and biological factors, such as scale, resources, timing, cell type, and how much — or how little — culture inspection and parameter control is required. Adherent platforms, such as flasks, are an entry point for many anchorage-dependent cell types, but they don't always support scale. Suspension platforms offer scalability, but adapting cells to suspension can be far more complex.

"It's not to say that one is particularly better than the other," says Hannah Gitschier, a Development Manager at Corning Life Sciences. "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."

Each system has pros and cons — and there are opportunities to get the best of both worlds. Here's what you should consider.

Advantages of Adherent Cell Culture Methods

Flasks, roller bottles, and other adherent cell culture vessels have the standout benefit of ease of use and option to provide anchorage-dependent cell types with biologically relevant surfaces.

"Most tissue-derived cells in the body require a surface or extracellular matrix to support growth and normal proliferation," Gitschier says. "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."

Some adherent platforms also have the benefit of visualization. Unlike bioreactors, you can easily view a flask or the bottom layers of a stacked vessel under a microscope.

"There are certain cell types where morphology is critical to indicating things beyond just cell health," Gitschier says. "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."

These advantages and others make adherent vessels a natural choice for many vaccine and cell and gene therapy programs, which tend to involve anchorage-dependent cell types. Adherent cultures also give the gift of time — a significant benefit for startups racing to get into the market.

"If there's steep competition to be the first to market, time could be one of those high-stake factors," Gitschier says. "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."

Advantages of Cell Suspension Culture Methods

Suspension methods range from small-scale vessels like Erlenmeyer and spinner flasks to large-scale stirred-tank bioreactors. For these approaches, the value is simple: You get yield scale. A lot of it.

That scalability and control makes suspension platforms an attractive option for manufacturers looking for operational efficiency in the lab.

But the trade-off could be more work up front. Researchers must adapt anchorage-dependent cell types to suspension environments. That takes time and effort.

"Anchorage-dependent cells might suffer from growth reduction and lower yields during adaptation," Gitschier says. "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."

Cell suspension cultures also lack the benefit of direct visualization, although other indicators and the benefit of having on-line and in-line process controls can tell you how you're doing.

"You still have ways of monitoring cell growth, like pH acidification and oxygen and glucose consumption," says Angel Garcia Martin, Ph.D., MBA, a business development manager at Corning Life Sciences. "Those are indirect measurements of culture growth, but you do lose the ability to look at the cells under a microscope."

Despite these challenges, suspension cultures can produce the high volume of cells needed for applications. The production of monoclonal antibodies using Chinese hamster ovary (CHO) cells is a classic example. Researchers adapted these cultures to thrive in a suspension environment — and now that's primarily how they're made.

But not every program needs that kind of scale. Autologous therapies and gene therapies targeting rare diseases or small patient population sizes may be produced sufficiently at smaller scale.

Getting the Benefits of Both

You can maximize the benefits of each method by utilizing next-generation technologies that provide more cell growth surface area within smaller, more manageable footprints for adherent cell culture, or lower shear stress for suspension cell culture.

That's the idea behind Corning® HYPERStack® technology, for example, which packs a greater number of layers into the same footprint as CellSTACK® cell culture vessels while maintaining gas exchange. Microcarriers provide the ability to scale with even greater surface area to volume ratio and offer pH and gas control by utilizing stirred-tank reactors. However, to take it to the next level, fixed bed bioreactors and emerging technology such as the Corning Ascent® Fixed Bed Reactor system enable both the increased surface area to volume ratio, while also allowing the cells to be immobilized and mitigating the risk of shear stress.

"When you start out, flasks or stacked vessels are a preferred option," Garcia Martin says. "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. "

But when it comes down to it, Gitschier and Garcia Martin agree: Your method depends on your 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," Gitschier says. "It's really about identifying what you want to get out of your platform and working from there."

You don't have to make the decision alone. Your equipment vendor or consumable manufacturer normally has field application experts who can help you determine which solution is best to support meeting your end goal. Contact your supplier to learn what worked best for similar labs and applications.