期刊
CELL STEM CELL
卷 10, 期 2, 页码 218-229出版社
CELL PRESS
DOI: 10.1016/j.stem.2012.01.003
关键词
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资金
- Leukemia and Lymphoma Society of Canada
- Canadian Stem Cell Network
- Canadian Institutes for Health Research [MOP-57885]
- Ontario Ministry of Research and Innovation
- NSERC
Clinical hematopoietic transplantation outcomes are strongly correlated with the numbers of cells infused. Anticipated novel therapeutic implementations of hematopoietic stem cells (HSCs) and their derivatives further increase interest in strategies to expand HSCs ex vivo. A fundamental limitation in all HSC-driven culture systems is the rapid generation of differentiating cells and their secreted inhibitory feedback signals. Herein we describe an integrated computational and experimental strategy that enables a tunable reduction in the global levels and impact of paracrine signaling factors in an automated closed-system process by employing a controlled fed-batch media dilution approach. Application of this system to human cord blood cells yielded a rapid (12-day) 11-fold increase of HSCs with self-renewing, multilineage repopulating ability. These results highlight the marked improvements that control of feedback signaling can offer primary stem cell culture and demonstrate a clinically relevant rapid and relatively low culture volume strategy for ex vivo HSC expansion.
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