Extracapillary space

Demetriou et al. [25] described a capillary hollow fiber membrane based bioreactor in which microcarrier-attached hepatocytes are placed in the extracapillary space on the exterior surface of the capillary hollow fiber membranes as shown in Fig. 1. Recent experimental studies with this device have demonstrated its efficacy in animal models. By using cryopreserved microcarrier-attached hepatocytes this system offers the convenience of being readily available when needed. 

If there are air bubbles in the extracapillary space, tilt the bioreactor to the vertical, so that they accumulate at the syringe access port (which will now be at the top) Open the tap of the syringe port only, and gently draw the air into the syringe. Close the tap. The reduced pressure created within the bioreactor will be compensated for by the flow of medium through the membranes (see Note 22). 

The core part of a hollow-fiber bioreactor is the hollow-fiber membrane module, also simply known as the cartridge. It consists of a plastic cylinder containing hundreds of semi-permeable capillary tubes, known as hollow fibers. The cells are inoculated in the extracapillary space (ECS). The cells colonize the external surface of the fibers and grow in this region. The culture medium is pumped through the lumen of the fibers, known as the intracapillary space (ICS), as shown in Figure 9.11. 

Simplified representation of a hollow-fiber module with only three fibers. The straight arrows pointing from the intracapillary space (ICS) to the extracapillary space (ECS) represent the transfer of nutrients from the culture medium to the cells (inoculated in the ECS), whereas the straight arrows in the opposite direction represent the transfer of metabolites and products from the cells to the fiber interior. 

The porous nature of the fibers allows for exchange of nutrients and metabolites. Low-molar-mass molecules, such as glucose and ammonia, can move freely through the pores of the fibers, at a rate that is controlled just by the pressure gradients generated by the medium recirculation pump. High-molar-mass proteins, which can be produced by the cells or added as nutritional supplements to the extracapillary space, are not able to permeate the membrane fibers and are retained in the cell bed in the ECS. 

Extracorporeal Hver assistance device (ELAD) Attention has recently focused on temporarily replacing the liver function with hepatocytes which have been cultured in the extracapillary space of a cellulose-acetate hollow-fibre unit. Each unit contains ca. 200 g C3A cells, an amount which is necessary for successful perfusion. ELAD has proved efficacious in clinical use. (106)... 

Perfusion MBRs have been introduced for the production of monoclonal antibodies. The mammalian cells that synthesize them are grown in the extracapillary space between the fibers in the module. Nutrients are supplied through the fibers, which also extract the metabolites continuously. The high cell concentrations between the fibers initiate high antibody harvests. These MBRs are also being investigated as an alternative concept for bioartificial organs such as liver and pancreas. 

Fig. 4 In situ recovery of urokinase from HT1080 cells growing in a hollow fiber reactor (HFR). Benzamidine Sepharose column is used to capture urokinase from the media circulating through the extracapillary space (ECS). A separate media reservoir is used to circulate media through the intracapillary space (ICS)...

Hollow-fiber reactors basically consist of a bunch of hollow fibers within a cartridge [107]. Cells are immobilized in the extracapillary space of the fibers. 

Horse chestnut extracts, notably aescin, have anti-inflammatory, antiedematous, antiexudative, and venotonic activities. The clinical pharmacology of horse chestnut and aescin has been the subject of many recent reviews. Aescin was found to be responsible for the antiexudative and edema-protective activity. Aescin acts on the capillary membrane, normalizing vascular permeability, enhancing capillary resistance, and reducing the outflow of fluid into the extracapillary space. Aescin has a sealing venotonic effect on the capillaries and reduces the number and diameter of the small pores of the capillary wall by which exchange of water occurs. In vitro. 

Similar to artificial kidneys, hoUow-fiber-based artificial liver devices can be developed by culturing living animal or human hepatocytes inside the hollow fibers and circulating the patient s blood in the extracapillary space. Toxic components in the blood that generally diffuse through the hollow fiber membrane are metabolized by the entrapped hepatocytes, and will then either diffuse back into the bloodstream or be washed out by the intraluminal stream. 

Labecki, M., Bowen, B. D., and Piret, J. M. (1996). Two-dimensional analysis of protein transport in the extracapillary space of hollow-fibre bioreactors. Chem. Eng. Sci. 51(17), 4197-4213. 

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