Exploring continuous and integrated strategies for the up- and downstream processing of human mesenchymal stem cells

Journal of Biotechnology
Bárbara CunhaPaula M Alves

Abstract

The integration of up- and downstream unit operations can result in the elimination of hold steps, thus decreasing the footprint, and ultimately can create robust closed system operations. This type of design is desirable for the bioprocess of human mesenchymal stem cells (hMSC), where high numbers of pure cells, at low volumes, need to be delivered for therapy applications. This study reports a proof of concept of the integration of a continuous perfusion culture in bioreactors with a tangential flow filtration (TFF) system for the concentration and washing of hMSC. Moreover, we have also explored a continuous alternative for concentrating hMSC. Results show that expanding cells in a continuous perfusion operation mode provided a higher expansion ratio, and led to a shift in cells' metabolism. TFF operated either in continuous or discontinuous allowed to concentrate cells, with high cell recovery (>80%) and viability (>95%); furthermore, continuous TFF permitted to operate longer with higher cell concentrations. Continuous diafiltration led to higher protein clearance (98%) with lower cell death, when comparing to discontinuous diafiltration. Overall, an integrated process allowed for a shorter process time, recovering 70% of ...Continue Reading

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Citations

Mar 1, 2016·Translational Research : the Journal of Laboratory and Clinical Medicine·P Gomes-AlvesP M Alves
Jun 21, 2015·Immunology Letters·C CapelliM Introna
Aug 17, 2016·Journal of Biotechnology·António M de SoureJoaquim M S Cabral
Sep 22, 2016·Stem Cells and Development·Parvaneh MohammadiNasser Aghdami
Jun 24, 2016·Tissue Engineering. Part B, Reviews·Toon LambrechtsIoannis Papantoniou
Apr 24, 2019·Nature Biomedical Engineering·Ayesha AijazBiju Parekkadan
Mar 14, 2021·Biotechnology and Bioengineering·Inês A IsidroMargarida Serra
May 1, 2021·Viruses·Francisca ArezPaula M Alves
Nov 18, 2017·ACS Applied Materials & Interfaces·Martina MiottoChe J Connon
Aug 14, 2021·Biotechnology and Bioengineering·Caroline SionEric Olmos

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