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Keywords:

  • neural precursor cells;
  • stem cells;
  • bioreactors;
  • scale-up;
  • shear;
  • oxygen transfer

Abstract

The clinical use of neural precursor cells (NPCs) for the treatment of neurological diseases, such as Parkinson's disease and Huntington's disease, requires overcoming the scarcity of these cells through controlled expansion. The main objective of the present study was to develop a large-scale computer-controlled bioprocess for the expansion of mammalian NPCs in suspension culture by scaling up existing reactor protocols. In order to support the oxygen demands of the maximum cell densities achieved, the volumetric mass transfer coefficient was kept above 1.10/h while scaling-up from small-scale 125 mL vessels to large-scale 500 mL bioreactors. In addition, the maximum shear stress at the impeller tip was maintained between 0.30 and 0.75 Pa to reduce damage to the cells. The resulting large-scale bioprocess achieved maximum viable cell densities of 1.2 × 106 cells/mL and a batch multiplication ratio of 9.1. Moreover, the process successfully maintained the NPC characteristics observed in small-scale studies. © 2006 Wiley Periodicals, Inc.