Journal home
Advance online publication
Current issue
Archive
Press releases
Supplements
Focuses
Guide to authors
Online submissionOnline submission
For referees
Free online issue
Contact the journal
Subscribe
Advertising
work@npg
Reprints and permissions
About this site
For librarians
 
NPG Resources
Nature
Nature Reviews
Nature Immunology
Nature Cell Biology
Nature Genetics
news@nature.com
Nature Conferences
Dissect Medicine
NPG Subject areas
Biotechnology
Cancer
Chemistry
Clinical Medicine
Dentistry
Development
Drug Discovery
Earth Sciences
Evolution & Ecology
Genetics
Immunology
Materials Science
Medical Research
Microbiology
Molecular Cell Biology
Neuroscience
Pharmacology
Physics
Browse all publications
Technical Report
Nature Medicine  9, 1423 - 1427 (2003)
Published online: 26 October 2003; | doi:10.1038/nm953

Ex vivo expansion of human hematopoietic stem cells by direct delivery of the HOXB4 homeoprotein

Sophie Amsellem1, Françoise Pflumio1, Dominique Bardinet1, Brigitte Izac1, Pierre Charneau2, Paul-Henri Romeo1, Anne Dubart-Kupperschmitt1 & Serge Fichelson1, 3

1  Institut Cochin, Département d'Hématologie, INSERM U567, CNRS UMR 8104, Université Paris 5, Maternité Port-Royal, 123, Bd de Port-Royal, 75014 Paris, France.

2  Unité d'Oncologie Virale, Institut Pasteur, 25−28 rue du Dr Roux, 75015 Paris, France.

3  AP-HP, Hôpital Cochin, 27 rue du Fg St Jacques, 75014 Paris, France.

Correspondence should be addressed to Serge Fichelson fichelson@cochin.inserm.fr
Expansion of human hematopoietic stem cells (HSCs) is a major challenge in cellular therapy, and currently relies on the use of recombinant cytokines or on gene transfer of transcription factors. Of these, the HOXB4 homeoprotein protein is of particular interests as it promotes the expansion of mouse HSCs without inducing the development of leukemia. To eliminate any deleterious effects that might be associated with stable HOXB4 gene transfer into human cells, we took advantage of the ability of HOX proteins to passively translocate through cell membranes. Here we show that when cultured on stromal cells genetically engineered to secrete HOXB4, human long-term culture-initiating cells (LTC-ICs) and nonobese diabetic−severe combined immunodeficiency (NOD-SCID) mouse repopulating cells (SRCs) were expanded by more than 20- and 2.5-fold, respectively, over their input numbers. This expansion was associated with enhanced stem cell repopulating capacity in vivo and maintenance of pluripotentiality. This method provides a basis for developing cell therapy strategies using expanded HSCs that are not genetically modified.

MORE ARTICLES LIKE THIS
These links to content published by NPG are automatically generated

REVIEWS
CD34+ or CD34-: which is the more primitive?
Leukemia Reviews (01 Sep 2002)
 See all 3 matches for Reviews

RESEARCH
Enforced expression of HOXB7 promotes hematopoietic stem cell proliferation and myeloid-restricted progenitor differentiation
Oncogene Original Article (18 Mar 1999)
Distinct classes of human stem cells that differ in proliferative and self-renewal potential
Nature Immunology Article (01 Jan 2001)
In vitro expansion of hematopoietic stem cells by recombinant TAT-HOXB4 protein
Nature Medicine null (01 Nov 2003)
Ex vivo expansion of CD34-positive peripheral blood progenitor cells from patients with non-Hodgkin's lymphoma: no evidence of concomitant expansion of contaminating bcl2/JH-positive lymphoma cells
Bone Marrow Transplantation Original Article (25 Aug 2000)
 See all 6 matches for Research

 Top
Abstract
Previous | Next
Table of contents
Full textFull text
Download PDFDownload PDF
Send to a friendSend to a friend
Figures & Tables
Supplementary info
Export citation
natureproducts

Search buyers guide:

 
ADVERTISEMENT
 
Nature Medicine
ISSN: 1078-8956
EISSN: 1546-170X
Journal home | Advance online publication | Current issue | Archive | Press releases | Supplements | Focuses | For authors | Online submission | For referees | Free online issue | About the journal | Contact the journal | Subscribe | Advertising | work@npg | Reprints and permissions | About this site | For librarians
Nature Publishing Group, publisher of Nature, and other science journals and reference works©2003 Nature Publishing Group | Privacy policy