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Differential Effects of HOXB4 on Nonhuman Primate Short- and Long-Term Repopulating Cells
BACKGROUND: Hematopoietic stem cells (HSCs) or repopulating cells are able to self-renew and differentiate into cells of all hematopoietic lineages, and they can be enriched using the CD34 cell surface marker. Because of this unique property, HSCs have been used for HSC transplantation and gene ther...
Autores principales: | , , , , , |
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Formato: | Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2006
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1450018/ https://www.ncbi.nlm.nih.gov/pubmed/16637742 http://dx.doi.org/10.1371/journal.pmed.0030173 |
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author | Zhang, Xiao-Bing Beard, Brian C Beebe, Katherine Storer, Barry Humphries, R. Keith Kiem, Hans-Peter |
author_facet | Zhang, Xiao-Bing Beard, Brian C Beebe, Katherine Storer, Barry Humphries, R. Keith Kiem, Hans-Peter |
author_sort | Zhang, Xiao-Bing |
collection | PubMed |
description | BACKGROUND: Hematopoietic stem cells (HSCs) or repopulating cells are able to self-renew and differentiate into cells of all hematopoietic lineages, and they can be enriched using the CD34 cell surface marker. Because of this unique property, HSCs have been used for HSC transplantation and gene therapy applications. However, the inability to expand HSCs has been a significant limitation for clinical applications. Here we examine, in a clinically relevant nonhuman primate model, the ability of HOXB4 to expand HSCs to potentially overcome this limitation. METHODS AND FINDINGS: Using a competitive repopulation assay, we directly compared in six animals engraftment of HOXB4GFP (HOXB4 green fluorescent protein) and control (yellow fluorescent protein [YFP])–transduced and expanded CD34 (+) cells. In three animals, cells were infused after a 3-d transduction culture, while in three other animals cells were infused after an additional 6–9 d of ex vivo expansion. We demonstrate that HOXB4 overexpression resulted in superior engraftment in all animals. The most dramatic effect of HOXB4 was observed early after transplantation, resulting in an up to 56-fold higher engraftment compared to the control cells. At 6 mo after transplantation, the proportion of marker gene–expressing cells in peripheral blood was still up to 5-fold higher for HOXB4GFP compared to YFP-transduced cells. CONCLUSIONS: These data demonstrate that HOXB4 overexpression in CD34 (+) cells has a dramatic effect on expansion and engraftment of short-term repopulating cells and a significant, but less pronounced, effect on long-term repopulating cells. These data should have important implications for the expansion and transplantation of HSCs, in particular for cord blood transplantations where often only suboptimal numbers of HSCs are available. |
format | Text |
id | pubmed-1450018 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2006 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-14500182006-05-30 Differential Effects of HOXB4 on Nonhuman Primate Short- and Long-Term Repopulating Cells Zhang, Xiao-Bing Beard, Brian C Beebe, Katherine Storer, Barry Humphries, R. Keith Kiem, Hans-Peter PLoS Med Research Article BACKGROUND: Hematopoietic stem cells (HSCs) or repopulating cells are able to self-renew and differentiate into cells of all hematopoietic lineages, and they can be enriched using the CD34 cell surface marker. Because of this unique property, HSCs have been used for HSC transplantation and gene therapy applications. However, the inability to expand HSCs has been a significant limitation for clinical applications. Here we examine, in a clinically relevant nonhuman primate model, the ability of HOXB4 to expand HSCs to potentially overcome this limitation. METHODS AND FINDINGS: Using a competitive repopulation assay, we directly compared in six animals engraftment of HOXB4GFP (HOXB4 green fluorescent protein) and control (yellow fluorescent protein [YFP])–transduced and expanded CD34 (+) cells. In three animals, cells were infused after a 3-d transduction culture, while in three other animals cells were infused after an additional 6–9 d of ex vivo expansion. We demonstrate that HOXB4 overexpression resulted in superior engraftment in all animals. The most dramatic effect of HOXB4 was observed early after transplantation, resulting in an up to 56-fold higher engraftment compared to the control cells. At 6 mo after transplantation, the proportion of marker gene–expressing cells in peripheral blood was still up to 5-fold higher for HOXB4GFP compared to YFP-transduced cells. CONCLUSIONS: These data demonstrate that HOXB4 overexpression in CD34 (+) cells has a dramatic effect on expansion and engraftment of short-term repopulating cells and a significant, but less pronounced, effect on long-term repopulating cells. These data should have important implications for the expansion and transplantation of HSCs, in particular for cord blood transplantations where often only suboptimal numbers of HSCs are available. Public Library of Science 2006-05 2006-05-02 /pmc/articles/PMC1450018/ /pubmed/16637742 http://dx.doi.org/10.1371/journal.pmed.0030173 Text en Copyright: © 2006 Zhang 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 Zhang, Xiao-Bing Beard, Brian C Beebe, Katherine Storer, Barry Humphries, R. Keith Kiem, Hans-Peter Differential Effects of HOXB4 on Nonhuman Primate Short- and Long-Term Repopulating Cells |
title | Differential Effects of HOXB4 on Nonhuman Primate Short- and Long-Term Repopulating Cells |
title_full | Differential Effects of HOXB4 on Nonhuman Primate Short- and Long-Term Repopulating Cells |
title_fullStr | Differential Effects of HOXB4 on Nonhuman Primate Short- and Long-Term Repopulating Cells |
title_full_unstemmed | Differential Effects of HOXB4 on Nonhuman Primate Short- and Long-Term Repopulating Cells |
title_short | Differential Effects of HOXB4 on Nonhuman Primate Short- and Long-Term Repopulating Cells |
title_sort | differential effects of hoxb4 on nonhuman primate short- and long-term repopulating cells |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1450018/ https://www.ncbi.nlm.nih.gov/pubmed/16637742 http://dx.doi.org/10.1371/journal.pmed.0030173 |
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