Scaled-Up Production of Mammalian Neural Precursor Cell Aggregates in Computer-Controlled Suspension Bioreactors
http://www3.interscience.wiley.com/cgi-bin/abstract/112446824/ABSTRACT?CRETRY=1&SRETRY=0
As a significant percentage of the population continues to grow older, the need for neurodegenerative therapies will likewise continue to grow. A very promising avenue of research is the use of neural precursor cells, or central nervous system stem cells, to repair and ideally cure central nervous system diseases such as Parkinson's disease. However, before cell-based therapies can be developed, there needs to be an substantial source of neural precursor cells available. So far, protocols to culture neural precursor cells exist only for small-scale bioreactors. In anticipation of the demand for neural precursor cells in the future, this group has decided to explore how to modify these existing protocols to scale-up production from a small-scale bioreactor to a large-scale computer-controlled bioreactor.
In scaling up the bioreactor vessel, adjustments must be made for changes in environment. Oxygen level is a primary concern for cell growth. Shear stress must also be maintained to prevent the cell aggregates from being damaged or from growing too large. Through equations and calculations from other studies, they concluded that these changes can be accounted for by adjusting the bioreactor's impeller to an appropriate rpm.
However, it was discovered that the fluid behavior of the system is altered by adding measuring probes into the system. These probes, otherwise unavailable for small-scale bioreactors, provide control over the bioreactor's pH, oxygen levels, and other environmental parameters. But with these probes, the hydrodynamic environment of the system was found to be drastically altered. Therefore, they adjusted the rpm of the impeller to create a similar hydrodynamic environment found in small-scale bioreactors, while at the same time maintain sufficient oxygen and shear stress levels.
Through the passages in the bioreactors that were performed, the group concluded that by adjusting the protocol to account for oxygen and shear stress level, as well as the hydrodynamic environment of the bioreactor vessels, adequate cell viability and cell density can be achieved in large-scale bioreactors. They however note that the cells require some time to adapt to the new environment. With this study, sufficient quantities of neural precursor cells can be generated to further fuel further studies to apply these cells for clinical uses.
2 comments:
It would be interesting to see where this research goes, especially for the production of dopaminergic cells. For example, Parkinson's can be attributed to the deterioration of the substantia nigra and its dopaminergic cells. So, hopefully these neural precursor cells can differentiate into dopaminergic cells to aid in treatments for Parkinson's.
It seems like another approach towards solving this problem would be to alter the design or placement of the bioreactor probes. That is to say, a redesign of the probes themselves could preserve fluid dynamics characteristics within the bioreactor and help maintain an appropriate level of shear stress without altering impeller RPM parameters.
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