Translational research projects are sometimes hampered by low productivity of an essential cell-secreted agent; this might be, for example, a monoclonal antibody, a cytokine or a more complex recombinant protein or perhaps even exosomes that need to be harvested from MSCs or another specific cell type. The incubator space dedicated to culture flasks for this scale of production can rapidly become a limiting factor and the amount of work required for cell passaging may also start to cause headaches. One solution could be to pass the work over to a services laboratory although, aside from the expense, outsourcing the production of a valuable and possibly confidential reagent may undesirable.

Escaping the low production conundrum

The only way to escape this conundrum is to find an efficient way to grow a lot more cells inside an existing incubator while leaving enough shelf space for other users. To be a viable method for an academic research laboratory, any such intensification of cell culture must fit the following criteria: easy to implement, not take up too much incubator space, easily commercially available, not too expensive to buy and operate, and, ideally, very well established and widely referenced.

Accelerating the pace with continuous high cell density

All the above criteria can be met with a well-designed hollow fibre bioreactor. A hollow fibre bioreactor makes it possible to continuously culture large numbers of cells at very high density. As in the body of an animal, maintaining a high density of cells is made possible because nutrients and oxygen are efficiently delivered while waste products are simultaneously removed. A hollow fibre bioreactor enables cells to grow in 3D layers around semi-permeable fibres that act as capillaries, offering a surface to volume ratio 100 x that of flasks. The selected fibre type will have a molecular weight cut-off tight enough to retain the target product which accumulates to high concentration. With a hollow fibre bioreactor repeated collections of product-enriched conditioned media are taken daily, or every few days in a process that can last many weeks. In this way, very large total amounts of product can be generated, for example, with a hybridoma 100 mg to 3 grams of antibody is possible in 12 weeks with a single cartridge.

The story behind hollow fibre technology

The first laboratory “artificial capillary bed” hollow fibre bioreactor was constructed in the 1970’s by the group of Richard Knazek at the NIH. A first paper showed L-929 cells growing as nodules around cellulosic fibre capillaries and was followed by other exciting papers confirming the potential for hollow fibre technology as a more in-vivo like way to grow cells. Subsequently, during the 80’s and 90’s, development of hollow fibre bioreactors was driven by the need to efficiently scale-up hybridoma culture. In the year 2000, the company FiberCell Systems Inc. was founded with the aim of making large scale production of valuable cell-secreted products achievable for any academic or commercial laboratory. The polysulfone fibres used in the FiberCell enabled much higher cell densities and more in-vivo like culture conditions to be achieved.

A  “workhorse” cell culture system

From 2001 to the 2020’s the FiberCell hollow fibre bioreactor has become a standard workhorse cell culture system, enabling a host of laboratories worldwide to accelerate important translational research projects. Many scientific publications now refer to this system with a recent flurry of academic papers re-confirming the value of this capillary-bed culture method for generating cell secretome and extracellular vesicles. Simultaneously an increasing number of commercial producers of monoclonal antibodies and recombinant proteins are exploiting the FiberCell bioreactor and are able to gain huge capacity by scaling-out the FiberCell platform, at a minimal cost compared to expensive tank or wave bioreactors while retaining an advantage for project flexibility, low media costs and higher product quality.

Further reading on this topic

Lists of publications that refer to the FiberCell bioreactor for production applications, by subject: