Cell retention

MCRT Mean Cell Retention Time - days. An expression of the average time that a microorganism will spend in an activated sludge process. 

Perfusion cultures of submerged free cells are essentially continuous cultures with a cell retention device so that no cells exit in the effluent stream. The governing ODEs are... 

The major drawback to using an intravenous route of cell delivery would be the possibility that the therapeutic cells would become trapped in the microvasculature of the lungs, liver, and lymphoid tissues. This theoretical limitation of systemic transvenous delivery of stem cells has been confirmed experimentally. In a study by Toma et al. [97], human MSCs were injected into the left ventricular cavity of experimental mice 4 days later, an estimated 0.44% of the injected cells remained in the myocardium, and the rest had localized to the spleen, liver, and lungs. Other studies using the systemic delivery approach have produced similar results, with very low local cell retention rates of less than 5% [98, 99]. Thus, the transvenous delivery route appears unlikely to achieve the local cell concentration needed to produce a significant therapeutic benefit. 

Cell Retention Devices for Suspended-Cell Perfusion Cultures... 

Keywords. Perfusion cultures, mammalian cell retention devices, filtration, centrifugation, sedimentation... 

From an economic point of view, perfusion cultures of animal cells should be operated at high perfusion rates [17]. However, the high cell concentrations achieved in such cases result in several technical constraints, such as oxygen transfer, CO2 removal, medium formulation, and, especially, cell retention efficiency. 

Centrifuges can be very efficient when separating cells from culture media. Consequently, they can be used either in harvesting of mammalian cells [1,21-23] or, despite their mechanical complexity, as cell retention device in long-term perfusion systems (Table 3). 

Table 3. Overview of reported perfusion processes employing centrifuges as cell retention device...

Himmelfarb et al. [80] introduced spin-filters as a cell retention device for high cell density perfusion cultivations of mammalian cells in suspension. Spin-filters are cylinders with a porous wall, which are placed inside stirred tank bioreactors, either mounted on the impeller shaft or driven by an independent motor (Fig. 5). Perfusate is pumped out from inside the spin-filter at the same... 

Besides fouling, cell retention efficiency is another important factor regarding spin-filter performance. A poor retention capacity of a spin-filter leads to a low apparent growth rate of the cell culture due to cell leakage (Eq. 10). 

Yabannavar et al. [81] used Eqs. (19) and (20) for scale-up purposes. Based on successful operation conditions determined for an existing 12-L bioreactor, they calculated the spin-filter dimensions and operation conditions for an existing 175-L bioreactor. Experiments with the spin-filter designed for the large-scale bioreactor resulted in an absence of filter clogging with cell retention efficiency similar to the 12-L bioreactor. This was considered as an evidence that the suggested scale-up strategy is adequate. 

Although perfusion cultures using RDF devices have not yet been reported, the results obtained in harvesting [113] and simulated perfusion experiments [104] indicate that it could be a promising cell retention device for suspendedcell perfusion processes. 

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