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Wnt3a Protein Reduces Growth Factor-Driven Expansion of Human Hematopoietic Stem and Progenitor Cells in Serum-Free Cultures

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...

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Autores principales: Duinhouwer, Lucia E., Tüysüz, Nesrin, Rombouts, Elwin W. J. C., ter Borg, Mariette N. D., Mastrobattista, Enrico, Spanholtz, Jan, Cornelissen, Jan J., ten Berge, Derk, Braakman, Eric
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4373922/
https://www.ncbi.nlm.nih.gov/pubmed/25807521
http://dx.doi.org/10.1371/journal.pone.0119086
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author Duinhouwer, Lucia E.
Tüysüz, Nesrin
Rombouts, Elwin W. J. C.
ter Borg, Mariette N. D.
Mastrobattista, Enrico
Spanholtz, Jan
Cornelissen, Jan J.
ten Berge, Derk
Braakman, Eric
author_facet Duinhouwer, Lucia E.
Tüysüz, Nesrin
Rombouts, Elwin W. J. C.
ter Borg, Mariette N. D.
Mastrobattista, Enrico
Spanholtz, Jan
Cornelissen, Jan J.
ten Berge, Derk
Braakman, Eric
author_sort Duinhouwer, Lucia E.
collection PubMed
description 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.
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spelling pubmed-43739222015-03-27 Wnt3a Protein Reduces Growth Factor-Driven Expansion of Human Hematopoietic Stem and Progenitor Cells in Serum-Free Cultures Duinhouwer, Lucia E. Tüysüz, Nesrin Rombouts, Elwin W. J. C. ter Borg, Mariette N. D. Mastrobattista, Enrico Spanholtz, Jan Cornelissen, Jan J. ten Berge, Derk Braakman, Eric PLoS One Research Article 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. Public Library of Science 2015-03-25 /pmc/articles/PMC4373922/ /pubmed/25807521 http://dx.doi.org/10.1371/journal.pone.0119086 Text en © 2015 Duinhouwer et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Duinhouwer, Lucia E.
Tüysüz, Nesrin
Rombouts, Elwin W. J. C.
ter Borg, Mariette N. D.
Mastrobattista, Enrico
Spanholtz, Jan
Cornelissen, Jan J.
ten Berge, Derk
Braakman, Eric
Wnt3a Protein Reduces Growth Factor-Driven Expansion of Human Hematopoietic Stem and Progenitor Cells in Serum-Free Cultures
title Wnt3a Protein Reduces Growth Factor-Driven Expansion of Human Hematopoietic Stem and Progenitor Cells in Serum-Free Cultures
title_full Wnt3a Protein Reduces Growth Factor-Driven Expansion of Human Hematopoietic Stem and Progenitor Cells in Serum-Free Cultures
title_fullStr Wnt3a Protein Reduces Growth Factor-Driven Expansion of Human Hematopoietic Stem and Progenitor Cells in Serum-Free Cultures
title_full_unstemmed Wnt3a Protein Reduces Growth Factor-Driven Expansion of Human Hematopoietic Stem and Progenitor Cells in Serum-Free Cultures
title_short Wnt3a Protein Reduces Growth Factor-Driven Expansion of Human Hematopoietic Stem and Progenitor Cells in Serum-Free Cultures
title_sort wnt3a protein reduces growth factor-driven expansion of human hematopoietic stem and progenitor cells in serum-free cultures
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4373922/
https://www.ncbi.nlm.nih.gov/pubmed/25807521
http://dx.doi.org/10.1371/journal.pone.0119086
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