HOXB4-induced expansion of adult hematopoietic stem cells ex vivo

Cell. 2002 Apr 5;109(1):39-45. doi: 10.1016/s0092-8674(02)00697-9.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Age Factors
  • Animals
  • Bone Marrow Cells / cytology
  • Bone Marrow Cells / metabolism
  • Bone Marrow Transplantation / methods
  • Cell Culture Techniques / methods*
  • Cell Division / drug effects
  • Cell Division / physiology*
  • Clone Cells / cytology
  • Clone Cells / drug effects
  • Clone Cells / metabolism
  • Female
  • Gene Expression Regulation, Developmental / drug effects
  • Gene Expression Regulation, Developmental / physiology
  • Graft Survival / drug effects
  • Graft Survival / physiology*
  • Hematopoietic Stem Cell Transplantation / methods*
  • Hematopoietic Stem Cells / cytology
  • Hematopoietic Stem Cells / drug effects
  • Hematopoietic Stem Cells / metabolism*
  • Homeodomain Proteins / metabolism*
  • Homeodomain Proteins / pharmacology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Transcription Factors / metabolism*
  • Transcription Factors / pharmacology
  • Transduction, Genetic / methods


  • Homeodomain Proteins
  • Hoxb4 protein, mouse
  • Transcription Factors