Differential effects of HOXB4 on nonhuman primate short- and long-term repopulating cells.

PLoS Medicine
Xiao-Bing ZhangHans-Peter Kiem

Abstract

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. 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-express...Continue Reading

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Citations

Mar 22, 2008·The Journal of Clinical Investigation·Xiao-Bing ZhangHans-Peter Kiem
Mar 22, 2008·The Journal of Clinical Investigation·Andre Larochelle, Cynthia E Dunbar
Sep 16, 2008·PloS One·Sabrina BondeNicholas Zavazava
Nov 29, 2013·Journal of Hematology & Oncology·Wenbin LiaoYupo Ma
Feb 20, 2010·International Journal of Hematology·Hiroshi SakamotoMinetaro Ogawa
Nov 24, 2011·Molecular Therapy : the Journal of the American Society of Gene Therapy·Xianmei MengXiao-Bing Zhang
Oct 16, 2007·Oncogene·B Argiropoulos, R K Humphries
Oct 18, 2011·Cytotherapy·Korashon Lynn WattsHans-Peter Kiem
Oct 8, 2008·American Journal of Hematology·Wu Hai-JiangDuan Hui-Jun
Sep 10, 2013·Seminars in Hematology·Andre Larochelle, Cynthia E Dunbar
Sep 1, 2015·Methods : a Companion to Methods in Enzymology·Christopher D PoradaGraça Almeida-Porada
Sep 26, 2013·Genomics, Proteomics & Bioinformatics·Xiao-Bing Zhang
May 13, 2017·Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation·Sandhya R PanchDavid F Stroncek
Sep 24, 2011·Expert Review of Hematology·Jerell R AguilaYupo Ma
Oct 22, 2016·Stem Cell Research & Therapy·Bin ShenYongping Jiang

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Methods Mentioned

BETA
leukapheresis
flow cytometry
PCR
FACS
electrophoresis

Software Mentioned

CellQuest

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