Clinical-scale expansion of CD34+ cord blood cells amplifies committed progenitors and rapid scid repopulation cells

Alba Casamayor-Genescà, Arnau Pla, Irene Oliver-Vila, Noèlia Pujals-Fonts, Sílvia Marín-Gallén, Marta Caminal, Irma Pujol-Autonell, Jorge Carrascal, Marta Vives-Pi, Joan Garcia, Joaquim Vives

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    1 Citation (Scopus)

    Abstract

    © 2016 Elsevier B.V. Umbilical cord blood (UCB) transplantation is associated with long periods of aplastic anaemia. This undesirable situation is due to the low cell dose available per unit of UCB and the immaturity of its progenitors. To overcome this, we present a cell culture strategy aimed at the expansion of the CD34+ population and the generation of granulocyte lineage-committed progenitors. Two culture products were produced after either 6 or 14 days of in vitro expansion, and their characteristics compared to non-expanded UCB CD34+ controls in terms of phenotype, colony-forming activity and multilineage repopulation potential in NOD-scid IL2Rγnull mice. Both expanded cell products maintained rapid SCID repopulation activity similar to the non-expanded control, but 14-day cultured cells showed impaired long term SCID repopulation activity. The process was successfully scaled up to clinically relevant doses of 89 × 106 CD34+ cells committed to the granulocytic lineage and 3.9 × 109 neutrophil precursors in different maturation stages. Cell yields and biological properties presented by the cell product obtained after 14 days in culture were superior and therefore this is proposed as the preferred production setup in a new type of dual transplant strategy to reduce aplastic periods, producing a transient repopulation before the definitive engraftment of the non-cultured UCB unit. Importantly, human telomerase reverse transcriptase activity was undetectable, c-myc expression levels were low and no genetic abnormalities were found, as determined by G-banding karyotype, further confirming the safety of the expanded product.
    Original languageEnglish
    Pages (from-to)19-29
    JournalNew Biotechnology
    Volume35
    DOIs
    Publication statusPublished - 25 Mar 2017

    Keywords

    • Aplasia
    • Bioreactor
    • CD34 +
    • Cell culture
    • Clinical scale
    • Hematopoietic stem cell transplantation
    • Umbilical cord blood

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