ABSTRACT
Packed-bed bioreactors provide
larger surface area to volume ratio compared to the static culture on flasks.
Therefore, these systems offer ideal production environment for large-scale
culture of mesenchymal stem cells (MSCs), but the effect of fluid dynamics on
the cell-behavior of MSCs is not fully elucidated. In this study, packed-bed
perfusion reactor loaded with different size of polymethyl methacrylate
carriers was used to apply different rates of shear stress and drug forces at
constant flow rate. The cell viability, cell-expansion, apoptosis and protein
secretion levels were analyzed for both unmodified and Vascular Endothelial
Growth Factor-positive (VEGF+) MSCs. The superficial stress was
estimated to between 0.21-0.25 N/m2. The results showed that the
shear stress reduced the VEGF secretion, and Caspase-3 was activated at high
drag force, which cause the reduction of the cell numbers in the bioreactor.
The reduction of cytoskeletal actin structures seemed to play the central role
in this adverse effect of the non-planar shear stress. The expression reduction of VEGF might also
have critical impacts on the tissue engineering applications, in which the
formation of vascular construct is essential.
Bioreactor Mesenchymal stem cells Packed bed column Protein secretion Vascular endothelial growth factor
ABSTRACT
Packed-bed bioreactors provide
larger surface area to volume ratio compared to the static culture on flasks.
Therefore, these systems offer ideal production environment for large-scale
culture of mesenchymal stem cells (MSCs), but the effect of fluid dynamics on
the cell-behavior of MSCs is not fully elucidated. In this study, packed-bed
perfusion reactor loaded with different size of polymethyl methacrylate
carriers was used to apply different rates of shear stress and drug forces at
constant flow rate. The cell viability, cell-expansion, apoptosis and protein
secretion levels were analyzed for both unmodified and Vascular Endothelial
Growth Factor-positive (VEGF+) MSCs. The superficial stress was
estimated to between 0.21-0.25 N/m2. The results showed that the
shear stress reduced the VEGF secretion, and Caspase-3 was activated at high
drag force, which cause the reduction of the cell numbers in the bioreactor.
The reduction of cytoskeletal actin structures seemed to play the central role
in this adverse effect of the non-planar shear stress. The expression reduction of VEGF might also
have critical impacts on the tissue engineering applications, in which the
formation of vascular construct is essential.
Bioreactor Mesenchymal stem cells Packed bed column Protein secretion Vascular endothelial growth factor
Primary Language | English |
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Subjects | Structural Biology |
Journal Section | Articles |
Authors | |
Publication Date | July 31, 2019 |
Published in Issue | Year 2019 |