Microcarrier

A microcarrier is a support matrix allowing for the growth of adherent cells in bioreactors.

In 1967, microcarrier development began when van Wezel found that microcarriers could support the growth of anchorage-dependent cells.[1] Microcarriers are typically 125 - 250 micrometre spheres and their density allows them to be maintained in suspension with gentle stirring. Microcarriers can be made from a number of different materials including DEAE-dextran, glass, polystyrene plastic, acrylamide, collagen, and alginate. These microcarrier materials, along with different surface chemistries, can influence cellular behavior, including morphology and proliferation.[2][3][4][5] Surface chemistries can include extracellular matrix proteins, recombinant proteins, peptides, and positively or negatively charged molecules.

Microcarriers are regularly used to grow protein-producing or virus-generating adherent cell populations in the large-scale commercial production of biologics (proteins) and vaccines.

Microcarrier cell culture is typically carried out in spinner flasks, although other vessels such as rotating wall microgravity bioreactors or fluidized bed bioreactors can also support microcarrier-based cultures. The advantages of microcarrier technology in the vaccine industry include (a) ease of scale-up, (b) ability to precisely control cell growth conditions in sophisticated, computer-controlled bioreactors, (c) an overall reduction in the floor space and incubator volume required for a given-sized manufacturing operation, and (d) a drastic reduction in technician labor.

Several types of microcarriers are available commercially including alginate-based (GEM, Global Cell Solutions), dextran-based (Cytodex, GE Healthcare), collagen-based (Cultispher, Percell), and polystyrene-based (SoloHill Engineering) microcarriers. They differ in their porosity, specific gravity, optical properties, presence of animal components, and surface chemistries.

Application

A liquid-based assembly method was developed by P. Chen et al. for assembling cell-seeded microcarriers into diverse structures. Neuron-seeded microcarriers were assembled for formation of 3D neural networks with controlled global shape. This method is potentially useful for tissue engineering and neuroscience.[6]

References

  1. van Wezel AL: Growth of cell-strains and primary cells on micro-carriers in Homogeneous culture. Nature 1967;216:64-65.
  2. Varani J, Dame M, Beals TF, Wass JA: Growth of three established cell lines on glass microcarriers. Biotechnol Bioeng 1983;25:1359-1372.
  3. Giard DJ, Thilly WG, Wang DI, Levine DW: Virus production with a newly developed microcarrier system. Appl Environ Microbiol 1977;34:668-672.
  4. Varani J, Dame M, Rediske J, Beals TF, Hillegas W: Substrate-dependent differences in growth and biological properties of fibroblasts and epithelial cells grown in microcarrier culture. J Biol Stand 1985;13:67-76.
  5. Varani J, Bendelow MJ, Chun JH, Hillegas WA: Cell growth on microcarriers: comparison of proliferation on and recovery from various substrates. J Biol Stand 1986;14:331-336.
  6. P. Chen, Z. Luo, S. Guven, S. Tasoglu, A. Weng, A. V. Ganesan, U. Demirci, Advanced Materials 2014, 10.1002/adma.201402079. http://onlinelibrary.wiley.com/doi/10.1002/adma.201402079/abstract


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