3-D Cell Culture

In many ways, the hollow fiber bioreactor may be considered the original 3-dimensional cell culture system. Hollow fiber bioreactors offer a method by which cells can be cultured at tissue-like densities over long periods of time.  Much new information has been gathered regarding hollow fiber bioreactors and it is now understood that they represent a fundamentally different and more in vivo-like way to culture cells.  It is one of the few ways to get two different cell types, at high enough densities, and for long enough periods of time to observe their effects on one another.  There is no question that the conditions under which cells are cultured have a profound effect on their behavior, and cell culture conditions are fundamentally different in a hollow fiber bioreactor.

Advantages to 3-D culture using hollow fiber

  • Reduction in apoptosis (Weeraphan, et al, 2012)
  • Consistency of culture over long periods of time (Pavlakis, 2013)
  • More in vivo-like growth conditions resulting in improved cell function (Bennet et al, 2007)
  • Facilitation of the use of serum-free, protein-free and chemically defined media formulations (Whitford and Cadwell, 2011)

Figure 1: Cardiac spheroids growing in 3-dimensions in hollow fiber bioreactor.

HF bioreactors provide many particular (and some unique) culture characteristics due to a number of physical and ambient chemical conditions provided by the system, including;

  • Perfused medium flow and porous support permits long-term culture
  • High cell density culture increases cell-to-cell contact
  • Selectable MWCO of fibers concentrates interactive cytokines
  • Selectable MWCO of fibers segregates cells, metabolites and products
  • Hydrodynamic (shear) force on endothelial cells required for proper physiology
  • Long-term high-density culture on porous support facilitates development of cell-to-cell interactions over time 

Hollow fiber bioreactors for cell co-cultivation

When considering the use of a hollow fiber bioreactor for cell co-cultivation the guiding principle is to recapitulate the in vivo environment and develop your model accordingly. If cell-to-cell communication is important then the C2008 5kd MWCO cartridge should be considered. If particular matrix proteins are important then the use of the C2025 PVDF cartridge will allow the binding of specific cytokines or matrix proteins. The C2025 should also be considered if the presence of endothelial cells under shear are an important component. Hollow fiber bioreactors are not a new technique, and many applications have been developed over the years.

  • Endothelial cell culture under shear, and in the presence of other cell types on the outside of the fibers, such as vascular smooth muscle, glial cells (for the blood-brain barrier model)
  • Endothelial cell culture under shear and interactions with circulating cells (cancer metastasis model.)
  • Bone marrow model
  • Placenta co-culture model
  • Gastric epithelium model for cryptosporidium culture
  • Antiviral pharmacokinetics

Hollow fiber bioreactors offer a unique opportunity to recapitulate the in vivo 3-D culture environment in your laboratory.