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Ex vivo expansion of cord blood haematopoietic stem/progenitor cells under physiological oxygen tensions: clear‐cut effects on cell proliferation, differentiation and metabolism
Author(s) -
Andrade Pedro Z.,
Soure António M.,
Santos Francisco,
Paiva Artur,
Cabral Joaquim M. S.,
Silva Cláudia L.
Publication year - 2015
Publication title -
journal of tissue engineering and regenerative medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.835
H-Index - 72
eISSN - 1932-7005
pISSN - 1932-6254
DOI - 10.1002/term.1731
Subject(s) - stem cell , progenitor cell , haematopoiesis , microbiology and biotechnology , cord blood , mesenchymal stem cell , ex vivo , cd34 , umbilical cord , chemistry , cd90 , andrology , immunology , biology , biochemistry , in vitro , medicine
Physiologically low O 2 tensions are believed to regulate haematopoietic stem cell (HSC) functions in the bone marrow (BM; 0–5%). In turn, placenta and umbilical cord are characterized by slightly higher physiological O 2 tensions (3–10%). We hypothesized that O 2 concentrations within this range may be exploited to augment the ex vivo expansion/maintenance of HSCs from umbilical cord (placental) blood (UCB). The expansion of UCB CD34 + ‐enriched cells was studied in co‐culture with BM mesenchymal stem/stromal cells (MSCs) under 2%, 5%, 10% and 21% O 2 . 2% O 2 resulted in a significantly lower CD34 + cell expansion (25‐fold vs 60‐, 64‐ and 92‐fold at day 10 for 5%, 21%, 10% O 2 , respectively). In turn, 10% O 2 promoted the highest CD34 + CD90 + cell expansion, reaching 22 ± 5.4‐ vs 5.6 ± 2.4‐ and 5.7 ± 2.0‐fold for 2%, 5% and 21% O 2 , respectively, after 14 days. Similar differentiation patterns were observed under different O 2 tensions, being primarily shifted towards the neutrophil lineage. Cell division kinetics revealed a higher proliferative status of cells cultured under 10% and 21% vs 2% O 2 . Expectedly, higher specific glucose consumption and lactate production rates were determined at 2% O 2 when compared to higher O 2 concentrations (5–21%). Overall, these results suggest that physiological oxygen tensions, in particular 10% O 2 , can maximize the ex vivo expansion of UCB stem/progenitor cells in co‐culture with BM MSCs. Importantly, these studies highlight the importance of exploiting knowledge of the intricate microenvironment of the haematopoietic niche towards the definition of efficient and controlled ex vivo culture systems capable of generating large HSCs numbers for clinical applications. Copyright © 2013 John Wiley & Sons, Ltd.