Limitations of Conventional Technology
While many stem cell therapies are being developed in clinical trials, few have resolved how production of the therapies can be scaled up to meet the needs of the market or even to make the therapies commercially viable.
For stem cell production, stirred bioreactors with micro-carriers are recognized to produce better results than two dimensional structures, however stem cells are easily damaged as a result of fluid turbulence in stirred bioreactors. Also, the cells frequently are not uniformly distributed throughout the bioreactor vessels, resulting in differing growth conditions for the cells in multiple mixing zones, which significantly undermines the integrity of the growth process.
Many scale up challenges can be mitigated through known process optimization techniques, though the greatest challenge, that of propagating cells in ever increasing sizes of conventionally equipped bioreactors, has as a primary obstacle, the laws of physics.
Conventionally equipped bioreactors incorporate axial flow impellers to create the agitation required to hold stem cells in suspension during their growth phase. Importantly, with conventionally equipped bioreactors, the impeller does the mixing. Though stem cells may survive agitation created by axial flow impellers in small bioreactor vessels, scaling up to larger vessels often requires the use of larger axial flow impellers to maintain cell suspension.
As the size of the axial flow impellers increase, the laws of physics dictate that speed at which the tip of the impellers move through the liquid, increases relative to the speed at which the hub of the impellers are turning. The velocity differentials along the axis of the impellers create hydrodynamic shear forces that can damage cells or even result in complete batch failure. For this reason, axial flow impellers are incompatible with effective scale up of stem cell production.