Culturing MSCs using the Quantum® cell expansion system
Bioreactors allow users to increase the scalability, automation, and reproducibility of their mesenchymal stem cell (MSC) cultures. Compared to traditional flask-cultured cells, bioreactors offer significant advantages, such as less user intervention, speed, streamlining processes, highly controllable environments, and occupying significantly less space. Therefore, they are particularly appropriate for the commercial production of clinical-grade MSCs.
Quantum® cell expansion system
There are various bioreactor platforms on the market. One of these is the Quantum® cell expansion system, a range of hollow fiber bioreactors from Terumo BCT. The Quantum® cell expansion system facilitates automation at all steps of the MSC culture workflow. These include cell seeding, reagent addition, feeding, and harvesting. All procedures are carried out in a closed environment, customizable and highly controllable, allowing users to easily track and adjust parameters depending on their needs and applications. Moreover, such close monitoring enables users to maintain high GMP compliance standards, including reporting, alarms, and recovery features.
Its hollow fiber design means the Quantum® system has a high surface area to volume ratio, saving on the cost of reagents and space. Likewise, the comprehensive platform replaces the incubators, biological safety cabinets, and clean rooms used in traditional cultural setups.
Does it work for MSC culture?
Studies have demonstrated the feasibility of large-scale expansion of MSCs using the Quantum® system1. Cultured cells retain tri-lineage differentiation potential, expression of typical biomarkers, and meet the standards for clinical applications (1,2).
A comprehensive study of MSCs from different sources also supported the application of the Quantum® platform for their expansion (3). The UK-based research group demonstrated that umbilical cord and bone marrow-derived MSCs met the criteria for MSCs, including the expression of surface markers, differentiation capacity, and adherent properties. Additionally, umbilical cord-derived MSCs cultured in the Quantum® bioreactor did not possess shortened telomeres, an undesirable by-product of their rapid proliferation that is mitigated by the reduced number of cell doublings required to reach large scale cultures in bioreactors (3).
Scientists also have a choice of different materials for coating the surface of the hollow fibers. These coatings are required for the uniform attachment of cells and are an essential component of reliable culture procedures. A recent study identified fibronectin, human cryoprecipitate, and recombinant human vitronectin as reliable coating materials for efficient MSC culture in the Quantum® system (4).
Overall, the Quantum® range of bioreactors represents an attractive system for expanding clinical MSCs on a large scale. Simultaneously improving the reliability of MSC cultures and minimizing costs, Quantum® is likely to be a valuable solution for cell therapies in the future.
References
1. Hanley, P. J. et al. Efficient manufacturing of therapeutic mesenchymal stromal cells with the use of the Quantum Cell Expansion System. Cytotherapy 16, 1048–1058 (2014) doi: 10.1016/j.jcyt.2014.01.417.
2. Russell, A. L., Lefavor, R. C. & Zubair, A. C. Characterization and cost–benefit analysis of automated bioreactor-expanded mesenchymal stem cells for clinical applications. Transfusion 58, 2374–2382 (2018) doi: 10.1111/trf.14805.
3. Mennan, C., Garcia, J., Roberts, S., Hulme, C. & Wright, K. A comprehensive characterisation of large-scale expanded human bone marrow and umbilical cord mesenchymal stem cells. Stem Cell Res. Ther. 10, (2019) doi: 10.1186/s13287-019-1202-4.
4. Frank, N. D., Jones, M. E., Vang, B. & Coeshott, C. Evaluation of reagents used to coat the hollow-fiber bioreactor membrane of the Quantum® Cell Expansion System for the culture of human mesenchymal stem cells. Mater. Sci. Eng. C 96, 77–85 (2019) doi: 10.1016/j.msec.2018.10.081.