Enhancing bone marrow regeneration by SALL4 protein

Hematopoietic stem cells (HSCs) are widely used in transplantation therapy to treat a variety of blood diseases. The success of hematopoietic recovery is of high importance and closely related to the patient’s morbidity and mortality after Hematopoietic stem cell transplantation (HSCT). We have prev...

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Main Authors: Liao, Wenbin, Aguila, Jerell R, Yao, Yixin, Yang, Jianchang, Zieve, Gary, Jiang, Yongping, Avila, Cecilia, Senzel, Lisa, Lai, Raymond, Xu, Dazhong, Dai, Wei, Ma, Yupo
Format: Online
Language:English
Published: BioMed Central 2013
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3882884/
id pubmed-3882884
recordtype oai_dc
spelling pubmed-38828842014-01-08 Enhancing bone marrow regeneration by SALL4 protein Liao, Wenbin Aguila, Jerell R Yao, Yixin Yang, Jianchang Zieve, Gary Jiang, Yongping Avila, Cecilia Senzel, Lisa Lai, Raymond Xu, Dazhong Dai, Wei Ma, Yupo Research Hematopoietic stem cells (HSCs) are widely used in transplantation therapy to treat a variety of blood diseases. The success of hematopoietic recovery is of high importance and closely related to the patient’s morbidity and mortality after Hematopoietic stem cell transplantation (HSCT). We have previously shown that SALL4 is a potent stimulator for the expansion of human hematopoietic stem/progenitor cells in vitro. In these studies, we demonstrated that systemic administration with TAT-SALL4B resulted in expediting auto-reconstitution and inducing a 30-fold expansion of endogenous HSCs/HPCs in mice exposed to a high dose of irradiation. Most importantly, TAT-SALL4B treatment markedly prevented death in mice receiving lethal irradiation. Our studies also showed that TAT-SALL4B treatment was able to enhance both the short-term and long-term engraftment of human cord blood (CB) cells in NOD/SCID mice and the mechanism was likely related to the in vivo expansion of donor cells in a recipient. This robust expansion was required for the association of SALL4B with DNA methyltransferase complex, an epigenetic regulator critical in maintaining HSC pools and in normal lineage progression. Our results may provide a useful strategy to enhance hematopoietic recovery and reconstitution in cord blood transplantation with a recombinant TAT-SALL4B fusion protein. BioMed Central 2013-11-05 /pmc/articles/PMC3882884/ /pubmed/24283261 http://dx.doi.org/10.1186/1756-8722-6-84 Text en Copyright © 2013 Liao et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 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.
repository_type Open Access Journal
institution_category Foreign Institution
institution US National Center for Biotechnology Information
building NCBI PubMed
collection Online Access
language English
format Online
author Liao, Wenbin
Aguila, Jerell R
Yao, Yixin
Yang, Jianchang
Zieve, Gary
Jiang, Yongping
Avila, Cecilia
Senzel, Lisa
Lai, Raymond
Xu, Dazhong
Dai, Wei
Ma, Yupo
spellingShingle Liao, Wenbin
Aguila, Jerell R
Yao, Yixin
Yang, Jianchang
Zieve, Gary
Jiang, Yongping
Avila, Cecilia
Senzel, Lisa
Lai, Raymond
Xu, Dazhong
Dai, Wei
Ma, Yupo
Enhancing bone marrow regeneration by SALL4 protein
author_facet Liao, Wenbin
Aguila, Jerell R
Yao, Yixin
Yang, Jianchang
Zieve, Gary
Jiang, Yongping
Avila, Cecilia
Senzel, Lisa
Lai, Raymond
Xu, Dazhong
Dai, Wei
Ma, Yupo
author_sort Liao, Wenbin
title Enhancing bone marrow regeneration by SALL4 protein
title_short Enhancing bone marrow regeneration by SALL4 protein
title_full Enhancing bone marrow regeneration by SALL4 protein
title_fullStr Enhancing bone marrow regeneration by SALL4 protein
title_full_unstemmed Enhancing bone marrow regeneration by SALL4 protein
title_sort enhancing bone marrow regeneration by sall4 protein
description Hematopoietic stem cells (HSCs) are widely used in transplantation therapy to treat a variety of blood diseases. The success of hematopoietic recovery is of high importance and closely related to the patient’s morbidity and mortality after Hematopoietic stem cell transplantation (HSCT). We have previously shown that SALL4 is a potent stimulator for the expansion of human hematopoietic stem/progenitor cells in vitro. In these studies, we demonstrated that systemic administration with TAT-SALL4B resulted in expediting auto-reconstitution and inducing a 30-fold expansion of endogenous HSCs/HPCs in mice exposed to a high dose of irradiation. Most importantly, TAT-SALL4B treatment markedly prevented death in mice receiving lethal irradiation. Our studies also showed that TAT-SALL4B treatment was able to enhance both the short-term and long-term engraftment of human cord blood (CB) cells in NOD/SCID mice and the mechanism was likely related to the in vivo expansion of donor cells in a recipient. This robust expansion was required for the association of SALL4B with DNA methyltransferase complex, an epigenetic regulator critical in maintaining HSC pools and in normal lineage progression. Our results may provide a useful strategy to enhance hematopoietic recovery and reconstitution in cord blood transplantation with a recombinant TAT-SALL4B fusion protein.
publisher BioMed Central
publishDate 2013
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3882884/
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