Differential effects of HOXB4 on nonhuman primate short- and long-term repopulating cells.
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
References
Deregulated expression of HOXB4 enhances the primitive growth activity of human hematopoietic cells.
Citations
The HOXB4 homeoprotein differentially promotes ex vivo expansion of early human lymphoid progenitors
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