Suspension or Adherent: Which Cell Culture Method Is Right for Your Lab?
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 choose an adherent or a suspension platform?
It depends.
The Options
The choice of a cell culture vessel is influenced by myriad operational and biological factors: scale, resources, timing, cell type, and how much — or how little — culture inspection and parameter control is required. Flasks and other adherent platforms 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 grow in suspension can be challenging.
"It's not to say that one is particularly better than the other," said 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 method has pros and cons, and there are ways to get the best of both. Here's what you should consider.
Advantages of Adherent Cell Culture Methods
Flasks, roller bottles, and other vessels for adherent cell culture offer ease of use and the 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 said. "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."
Adherent platforms may also have the benefit of visualization. Using an inverted microscope, you can view growth on flask surfaces or the bottom layers of stacked vessels.
"There are certain cell types where morphology is critical to indicating things beyond just cell health," Gitschier said. "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 and other advantages make adherent methods a natural choice for many vaccine, cell therapy, and gene therapy programs, which tend to be based on 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 said. "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 method vessels range from small-scale 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 who want to gain operational efficiency. 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 explained. "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 you can still monitor progress using other indicators as well as on-line and in-line process controls.
"You still have ways of monitoring cell growth, like pH acidification and oxygen and glucose consumption," said Angel Garcia Martin, PhD, 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."
Suspension cultures can produce the high volume of cells needed for applications, despite the challenges. The production of monoclonal antibodies using Chinese hamster ovary (CHO) cells is a classic example. Researchers adapted these cells to thrive in a suspension environment, and it has become the primary method of production.
However, 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.
Get the Benefits of Both
You can maximize the benefits of each method with next-generation technologies. Get more growth surface area within smaller and more manageable adherent culture vessels or reduce shear stress levels in suspension cell cultures.
That's the idea behind Corning HYPERStack vessels, which adds more layers into the same footprint as CellSTACK cell culture vessels while maintaining adequate gas exchange.
Microcarriers let you scale with even greater surface area-to-volume ratio and offer pH and gas control with stirred-tank reactors. Taking it to the next level, fixed-bed bioreactors and the emerging technology of Corning Ascent Fixed Bed Reactor systems increase the surface area-to-volume ratio while also immobilizing the cells to mitigate the risks of shear stress.
"When you start out, flasks or stacked vessels are a preferred option," Garcia Martin said. "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."
In the end, Gitschier and Garcia Martin agree: The 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 said. "It's really about identifying what you want to get out of your platform and working from there."
But you don't have to make the decision alone. Consult with your equipment or culture vessel manufacturer or supplier. Their field application experts can help you determine which solution may best support your end goals based on their experiences with similar labs and applications.
