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Biotechnol Bioeng. 2018 Jul;115(7):1717-1728. doi: 10.1002/bit.26601. Epub 2018 Apr 10.

Hollow microcarriers for large-scale expansion of anchorage-dependent cells in a stirred bioreactor.

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Division of Electrical and Computer Engineering, Louisiana State University, Baton Rouge, Louisiana.
Bioengineering Graduate Program, University of Notre Dame, Notre Dame, Indiana.
Department of Electrical and Computer Engineering, University of New Hampshire, Durham, New Hampshire.
Department of Aerospace and Mechanical Engineering, University of Notre Dame, Notre Dame, Indiana.


With recent advances in biotechnology, mammalian cells are used in biopharmaceutical industries to produce valuable protein therapeutics and investigated as effective therapeutic agents to permanently degenerative diseases in cell based therapy. In these exciting and actively expanding fields, a reliable, efficient, and affordable platform to culture mammalian cells on a large scale is one of the most vital necessities. To produce and maintain a very large population of anchorage-dependent cells, a microcarrier-based stirred tank bioreactor is commonly used. In this approach, the cells are exposed to harmful hydrodynamic shear stress in the bioreactor and the mass transfer rates of nutrients and gases in the bioreactor are often kept below an optimal level to prevent cellular damages from the shear stress. In this paper, a hollow microcarrier (HMC) is presented as a novel solution to protect cells from shear stress in stirred bioreactors, while ensuring sufficient and uniform mass transfer rate of gases and nutrients. HMC is a hollow microsphere and cells are cultured on its inner surface to be protected, while openings on the HMC provide sufficient exchange of media inside the HMC. As a proof of concept, we demonstrated the expansion of fibroblasts, NIH/3T3 and the expansion and cardiac differentiation of human induced pluripotent stem cells, along with detailed numerical analysis. We believe that the developed HMC can be a practical solution to enable large-scale expansion of shear-sensitive anchorage-dependent cells in an industrial scale with stirred bioreactors.


anchorage-dependent cells; hiPSC; large-scale expansion; microcarriers; shear stress

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