Nature Medicine9, 1428 - 1432 (2003)
Published online: 26 October 2003; | doi:10.1038/nm951
In vitro expansion of hematopoietic stem cells by recombinant TAT-HOXB4 protein
Jana Krosl1, 5, Pamela Austin1, 5, Nathalie Beslu1, 5, Evert Kroon1, 5, R Keith Humphries2
& Guy Sauvageau1, 3, 4, 5
1
Laboratory of Molecular Genetics of Hemopoietic Stem Cells, Clinical Research Institute of Montreal, Montreal, Quebec, Canada, H2W 1R7.
2
Terry Fox Laboratory, British Columbia Cancer Agency, Vancouver, British Columbia, Canada, V5Z 1L3.
3
Department of Medicine and Division of Hematology, Hospital Maisonneuve-Rosemont, Montreal, Quebec, Canada, H1T 2M4.
4
Montreal University, Montreal, Quebec, Canada, H3C 3J7.
5
Present address: Institute of Research in Immunology and Cancer, University of Montreal, CP 6128, Downtown Station, Montreal, Quebec, Canada, H3C 3J7.
Hematopoietic stem cells (HSCs) can self-renew extensively after transplantation. The conditions supporting their in vitro expansion are still being defined. Retroviral overexpression of the human homeobox B4 (HOXB4) gene in mouse bone marrow cells enables over 40-fold expansion of HSCs in vitro. To circumvent the requirement for retroviral infection, we used recombinant human TAT-HOXB4 protein carrying the protein transduction domain of the HIV transactivating protein (TAT) as a potential growth factor for stem cells. HSCs exposed to TAT-HOXB4 for 4 d expanded by about four- to sixfold and were 8−20 times more numerous than HSCs in control cultures, indicating that HSC expansion induced by TAT-HOXB4 was comparable to that induced by the human HOXB4 retrovirus during a similar period of observation. Our results also show that TAT-HOXB4-expanded HSC populations retain their normal in vivo potential for differentiation and long-term repopulation. It is thus feasible to exploit recombinant HOXB4 protein for rapid and significant ex vivo expansion of normal HSCs.
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