Large-scale production of stem cells utilizing microcarriers: A biomaterials engineering perspective from academic research to commercialized products

Microcarriers for Upscaling Cultured Meat Production

“…In a similar way to thermo-responsive polymers, the unique properties of pH, photo or electric current responsive polymers can be harnessed to create smart microcarriers for cell detachment from MCs, however, research on those materials is still at early stages and sometimes difficult to combine with cell culture, thus MCs with such responsivity have not been reported yet (142).…”

Microfluidic‐Printed Microcarrier for In Vitro Expansion of Adherent Stem Cells in 3D Culture Platform

“…A literature survey indicated that plastic spherical microcarriers are an optimal choice for the scale‐up manufacturing of postnatal stem cells; however, a major shortcoming of plastic spherical microcarriers—monitoring difficulties—impedes the effective application and utilization of 3D expansion culture platforms in actual manufacturing practice. The reliable observation of cells along the 3D spherical contours of commercial microcarriers could be achieved by adapting newly developed equipment, such as imaging devices for high content screening (HCS), to the task, providing imaging results similar to those obtained from 3D cell spheres .…”

“…The mass production of allogeneic stem‐cell‐based therapeutic agents requires the development of effective expansion culture processes. To meet this need, a variety of in vitro scale‐up culture systems and bioreactors have been developed, including stacked multi‐plate 2D culture platforms, such as the Cell Factory and Xpansion; fixed‐bed bioreactors, such as hollow fibers and iCELLis; and bioreactors for microcarrier‐based 3D cultures, such as Vertical‐Wheel bioreactors and spinner flasks . Adherent stem cells require attachment surfaces for cell proliferation; therefore, the scale‐up of postnatal stem cell cultures must involve a system with a high surface/volume ratio.…”

“…A recent analysis of the experimental processes, cost efficiency, and robustness of adherent cell culture technologies suggested that multi‐layered 2D culture vessels and stirred tank bioreactors with microcarriers could potentially replace conventional 2D culture platforms . Several thorough comparative investigations also indicated that microcarrier‐based 3D cultures provide the most efficient method for the in vitro expansion culturing of adherent cells, not only due to the volume economy arising from the high surface/volume ratio, but also due to the effectiveness of handling large numbers of cultured cells . These considerations elevated plastic microcarriers as the optimal choice for the scale‐up culture of postnatal stem cells, such as hMSCs.…”

A genomic biomarker that identifies human bone marrow-derived mesenchymal stem cells with high scalability

“…Prior knowledge of GSTT1 status may be helpful for autologous therapy as well, as strategies could be developed to increase the scalability of hMSCs retaining one or more copy of the gene. When combined with other improvements in MSC bioprocessing, such as microcarriers 63,64 and media formulations, 65,66 the production of billions of stem cells with high therapeutic potency may become a reality, so helping to provide relief to the growing health and economic burden of an ever‐aging population.…”