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Ex-vivo expansion of nonhuman primate CD34(+) cells by stem cell factor Sall4B
BACKGROUND: Hematopoietic CD34(+) stem cells are widely used in the clinical therapy of complicated blood diseases. Stem cell factor Sall4B is a zinc finger transcription factor that plays a vital role in hematopoietic stem cell expansion. The purpose of our current study is to further evaluate how...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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BioMed Central
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5072326/ https://www.ncbi.nlm.nih.gov/pubmed/27765075 http://dx.doi.org/10.1186/s13287-016-0413-1 |
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author | Shen, Bin Zhang, Yu Dai, Wei Ma, Yupo Jiang, Yongping |
author_facet | Shen, Bin Zhang, Yu Dai, Wei Ma, Yupo Jiang, Yongping |
author_sort | Shen, Bin |
collection | PubMed |
description | BACKGROUND: Hematopoietic CD34(+) stem cells are widely used in the clinical therapy of complicated blood diseases. Stem cell factor Sall4B is a zinc finger transcription factor that plays a vital role in hematopoietic stem cell expansion. The purpose of our current study is to further evaluate how Sall4B might affect the expansion of CD34(+) cells derived from nonhuman primates. METHODS: Sall4B was overexpressed in nonhuman primate bone marrow-derived CD34(+) cells via a lentiviral transduction system. The granulocyte–erythrocyte–macrophage–megakaryocyte colony-forming unit (CFU) assay evaluated the differentiation potential of primate CD34(+) cells that were expanded with Sall4B. Furthermore, an in-vivo murine system was employed to evaluate the hematopoietic potential of primate Sall4B-expanded CD34(+) cells. RESULTS: Overexpression of Sall4B promoted ex-vivo nonhuman primate CD34(+) cell expansion by 9.21 ± 1.94-fold on day 9, whereas lentiviral transduction without Sall4B expanded cells by only 2.95 ± 0.77-fold. Sall4B maintained a significant percentage of CD34(+) cells as well. The CFU assay showed that the Sall4B-expanded CD34(+) cells still possessed multilineage differentiation potential. A study using nonobese diabetic/severe combined immunodeficiency (NOD/SCID) mice in vivo revealed that Sall4B led to an increase in the number of repopulating cells and the 9-day-old Sall4B-transduced CD34(+) cells still possess self-renewal and multilineage differentiation capacity in vivo, which are similar stemness characteristics to those in freshly isolated primate bone marrow-derived CD34(+) cells. CONCLUSIONS: We investigated the expansion of nonhuman primate bone marrow-derived CD34(+) cells using the Sall4B lentiviral overexpression approach; our findings provide a new perspective on mechanisms of rapid stem cell proliferation. The utilization of Sall4B to expand CD34(+) cells on a large scale through use of suitable model systems would prove helpful towards preclinical trials of autologous transplantation. |
format | Online Article Text |
id | pubmed-5072326 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-50723262016-10-24 Ex-vivo expansion of nonhuman primate CD34(+) cells by stem cell factor Sall4B Shen, Bin Zhang, Yu Dai, Wei Ma, Yupo Jiang, Yongping Stem Cell Res Ther Research BACKGROUND: Hematopoietic CD34(+) stem cells are widely used in the clinical therapy of complicated blood diseases. Stem cell factor Sall4B is a zinc finger transcription factor that plays a vital role in hematopoietic stem cell expansion. The purpose of our current study is to further evaluate how Sall4B might affect the expansion of CD34(+) cells derived from nonhuman primates. METHODS: Sall4B was overexpressed in nonhuman primate bone marrow-derived CD34(+) cells via a lentiviral transduction system. The granulocyte–erythrocyte–macrophage–megakaryocyte colony-forming unit (CFU) assay evaluated the differentiation potential of primate CD34(+) cells that were expanded with Sall4B. Furthermore, an in-vivo murine system was employed to evaluate the hematopoietic potential of primate Sall4B-expanded CD34(+) cells. RESULTS: Overexpression of Sall4B promoted ex-vivo nonhuman primate CD34(+) cell expansion by 9.21 ± 1.94-fold on day 9, whereas lentiviral transduction without Sall4B expanded cells by only 2.95 ± 0.77-fold. Sall4B maintained a significant percentage of CD34(+) cells as well. The CFU assay showed that the Sall4B-expanded CD34(+) cells still possessed multilineage differentiation potential. A study using nonobese diabetic/severe combined immunodeficiency (NOD/SCID) mice in vivo revealed that Sall4B led to an increase in the number of repopulating cells and the 9-day-old Sall4B-transduced CD34(+) cells still possess self-renewal and multilineage differentiation capacity in vivo, which are similar stemness characteristics to those in freshly isolated primate bone marrow-derived CD34(+) cells. CONCLUSIONS: We investigated the expansion of nonhuman primate bone marrow-derived CD34(+) cells using the Sall4B lentiviral overexpression approach; our findings provide a new perspective on mechanisms of rapid stem cell proliferation. The utilization of Sall4B to expand CD34(+) cells on a large scale through use of suitable model systems would prove helpful towards preclinical trials of autologous transplantation. BioMed Central 2016-10-20 /pmc/articles/PMC5072326/ /pubmed/27765075 http://dx.doi.org/10.1186/s13287-016-0413-1 Text en © The Author(s). 2016 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Shen, Bin Zhang, Yu Dai, Wei Ma, Yupo Jiang, Yongping Ex-vivo expansion of nonhuman primate CD34(+) cells by stem cell factor Sall4B |
title | Ex-vivo expansion of nonhuman primate CD34(+) cells by stem cell factor Sall4B |
title_full | Ex-vivo expansion of nonhuman primate CD34(+) cells by stem cell factor Sall4B |
title_fullStr | Ex-vivo expansion of nonhuman primate CD34(+) cells by stem cell factor Sall4B |
title_full_unstemmed | Ex-vivo expansion of nonhuman primate CD34(+) cells by stem cell factor Sall4B |
title_short | Ex-vivo expansion of nonhuman primate CD34(+) cells by stem cell factor Sall4B |
title_sort | ex-vivo expansion of nonhuman primate cd34(+) cells by stem cell factor sall4b |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5072326/ https://www.ncbi.nlm.nih.gov/pubmed/27765075 http://dx.doi.org/10.1186/s13287-016-0413-1 |
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