Tostoes, R;
Dodgson, J;
Weil, B;
Gerontas, S;
Mason, C;
Veraitch, FS;
(2017)
A novel filtration system for point of care washing of cellular therapy products.
Journal of Tissue Engineering and Regenerative Medicine
, 11
(11)
pp. 3157-3167.
10.1002/term.2225.
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Abstract
The cell therapy industry would greatly benefit from a simple point of care solution to remove Dimethyl Sulfoxide (DMSO) from small volume thawed cell suspensions prior to injection. We have designed and validated a novel dead-end filtration device, which takes advantage of the higher density of thawed cell suspensions to remove the DMSO and protein impurities from the cell suspension without fouling the filter membrane. The filter was designed to avoid fluid circuits and minimize the surface area that is contacted by the cell suspension, thus reducing cell losses by design. The filtration process was established through optimization of the fluid flow configuration, backflush cycles and filter geometry. Overall, this novel filtration device allows for a 1 mL of thawed cryopreserved cell suspensions, containing 107 cells of a foetal lung fibroblast cell line (MRC-5), to be washed in less than 30 minutes. More than 95% of the DMSO and up to 94% of the Albumin- Fluorescein-Isothiocyanate content can be removed while the viable cell recovery is higher than 80%. We have also demonstrated that this system can be used for bone marrow-derived human mesenchymal stem cells with more than 73% cell recovery and 85% DMSO reduction. This is the first time that a dead end (normal) filtration process has been used to successfully wash high density human cell suspensions. In practice, this novel solid-liquid separation technology fills the need for small volume washing in closed processing systems for cellular therapies.
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