1. Wnt3a protein reduces growth factor-driven expansion of human hematopoietic stem and progenitor cells in serum-free cultures
- Author
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Duinhouwer, Lucia E., Tüysüz, Nesrin, Rombouts, Elwin W J C, Ter Borg, Mariette N D, Mastrobattista, Enrico, Spanholtz, Jan, Cornelissen, Jan J., Berge, Derk Ten, Braakman, Eric, Sub Drug delivery, UIPS - Utrecht Institute for Pharmaceutical Sciences, Pharmaceutics, Sub Drug delivery, UIPS - Utrecht Institute for Pharmaceutical Sciences, Pharmaceutics, Hematology, and Cell biology
- Subjects
Cellular differentiation ,medicine.medical_treatment ,CD34 ,lcsh:Medicine ,Antigens, CD34 ,Biology ,Biochemistry ,Culture Media, Serum-Free ,Glycogen Synthase Kinase 3 ,Mice ,Mice, Inbred NOD ,Wnt3A Protein ,medicine ,Animals ,Humans ,Cell Lineage ,Progenitor cell ,lcsh:Science ,Wnt Signaling Pathway ,Cells, Cultured ,beta Catenin ,Medicine(all) ,Multidisciplinary ,Agricultural and Biological Sciences(all) ,Biochemistry, Genetics and Molecular Biology(all) ,Growth factor ,Stem Cells ,lcsh:R ,Wnt signaling pathway ,Hematopoietic Stem Cell Transplantation ,Cell Differentiation ,Parkinson Disease ,Fetal Blood ,Hematopoietic Stem Cells ,Cell biology ,Haematopoiesis ,Receptors, Aryl Hydrocarbon ,Liposomes ,lcsh:Q ,Stem cell ,Research Article ,Genetics and Molecular Biology(all) - Abstract
Ex vivo expansion of hematopoietic stem and progenitor cells (HSPC) is a promising approach to improve insufficient engraftment after umbilical cord blood stem cell transplantation (UCB-SCT). Although culturing HSPC with hematopoietic cytokines results in robust proliferation, it is accompanied with extensive differentiation and loss of self-renewal capacity. Wnt signaling has been implicated in regulating HSPC fate decisions in vivo and in promoting HSPC self-renewal by inhibition of differentiation, but the effects of Wnt on the ex vivo expansion of HSPC are controversial. Here, we demonstrate that exogenous Wnt3a protein suppresses rather than promotes the expansion of UCB-derived CD34(+) cells in serum free expansion cultures. The reduced expansion was also observed in cultures initiated with Lin(-)CD34(+)CD38(low)CD45RA(-)CD90(+) cells which are highly enriched in HSC and was also observed in response to activation of beta-catenin signaling by GSK3 inhibition. The presence of Wnt3a protein during the culture reduced the frequency of multilineage CFU-GEMM and the long-term repopulation ability of the expanded HSPC. These data suggest that Wnt signaling reduces expansion of human HSPC in growth factor-driven expansion cultures by promoting differentiation of HSPC.
- Published
- 2015