In bioprocessing, higher production volume is a crucial goal. Ang-Chen Tsai, PhD, senior scientist at WuXi Advanced Therapies, and Christina Pacak, PhD, assistant professor of neurology at the University of Minnesota Medical School, reported that more human mesenchymal stem cells (hMSCs) can be produced with a microcarrier-based bioreactor compared to traditional planar cultures.
In a microcarrier-based bioreactor, small beads—microcarriers—serve as the substrate for the hMSCs. The cells “adhere and grow at a very high surface-to-volume ratio, thus supporting the highest volumetric cell productivity,” Pacak explains. “When maintained in suspension using bioreactor agitation, the cells growing upon microcarriers are exposed to a consistent, homogeneous, and more controllable nutrition and oxygen supply.”
Plus, it’s easier and less expensive to scale up a microcarrier-based bioreactor system than it is with a planar-culture approach. So, Pacak says, “Microcarrier-based bioreactors provide a more profitable approach to manufacturing hMSCs for cell-therapy applications.”
A microcarrier-based bioreactor offers many advantages in growing hMSCs. For one thing, Tsai points out the “hMSCs secrete high amounts of extracellular matrix, which enhances their adhesion on microcarriers.” In addition, hMSCs are sensitive to their microenvironment, and microcarrier-based bioreactors provide cells with a consistent and well-mixed culture environment, plus precise control of the temperature, pH, and dissolved oxygen. “This consistency is important to prevent hMSC differentiation during expansion,” Tsai notes.
Last, a microcarrier-based bioreactor allows real-time off-line monitoring of cell growth and quality, plus metabolite analyses, which can be used to detect and correct errors immediately.
When asked how a commercial bioprocessor can make use of this technology, Pacak tells GEN, “Easily,” adding that “bioreactors are already commonly used for cell production in upstream processes, but the challenge lies in the combined use of microcarriers in bioreactors due to cell adhesion and detachment methodologies, and this is surmountable.”
Even now, numerous studies have explored the use of commercial microcarriers for hMSC expansion, and the techniques have been optimized.
“For cell detachment, if the purpose is to collect hMSCs for clinical transplantation, careful detachment and separation of cells from the microcarriers is critical and must be optimized for each system,” Tsai says. “If the purpose is to harvest hMSC-secreted products, such as extracellular vesicles, then the removal of microcarriers from cells is not necessary.”
The microcarrier method offers great promise in increasing the production of stem cells to develop cell-based therapies.
“Taken together, commercial bioreactors and microcarriers can be used for hMSC manufacturing, but process optimizations geared towards the specific downstream product are required,” concludes Pacak.
