Peter Zandstra, Professor of Tissue Engineering at the University of Toronto, kindly provided this article on âRapid expansion of human hematopoietic stem cells by automated control of inhibitory feedback signaling.' Peter co-authored this article, which was published in Cell Stem Cell.
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 HSCdriven 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.
Peter will be presenting at this year's World Cord Blood Congress, on the topic, âImprovements in HSC expansion towards rapid multilineage repopulating ability.' Register now to hear him share his expertise on this subject matter.