HOXB4-induced expansion of adult hematopoietic stem cells ex vivo

Abstract

Hox transcription factors have emerged as important regulators of primitive hematopoietic cell proliferation and differentiation. In particular, HOXB4 appears to be a strong positive regulator of hematopoietic stem cell (HSC) self-renewal. Here we demonstrate the potency of HOXB4 to enable high-level ex vivo HSC expansion. Cultures of nontransduced or GFP-transduced murine bone marrow cells experienced large HSC losses over 10-14 days. In sharp contrast, cultures of HOXB4-transduced cells achieved rapid, extensive, and highly polyclonal HSC expansions, resulting in over 1000-fold higher levels relative to controls and a 40-fold net HSC increase. Importantly, these HSCs retained full lympho-myeloid repopulating potential and enhanced in vivo regenerative potential, demonstrating the feasibility of achieving significant ex vivo expansion of HSCs without functional impairment.