Effects of hydrodynamics on cultures of mammalian neural stem cell aggregates in suspension bioreactors

Mammalian neural stem cells hold great promise for the treatment of central nervous system disorders. However, to be a viable clinical treatment for t he millions of individuals afflicted with these disorders, it is necessary to develop cell expansion protocols. Although difficult to grow in bioreact ors, neural stem cells can be expanded, in carefully designed media as aggr egates of brain tissue. The objective of this study was to examine the cont rol of the aggregate size in a batch culture by manipulating the agitation rate, and hence the liquid shear and oxygen transfer rate, in bioreactors. This is very important because large aggregates can develop necrotic center s of dead cells due to transport limitations of key nutrients. Manipulation of the agitation rate allowed us to control the average aggregate diameter to 150 mum, below levels where necrosis would occur. Moreover, for the bes t conditions, viable stem cell densities of 1.2 x 10(6) cells/mL were achie ved in a batch culture with viabilities remaining above 80% for the majorit y of the runs.