Involvement of insulin-like growth factor-I and insulin-like growth factor binding proteins in pro-B-cell development

Exp Hematol. 2006 Apr;34(4):508-18. doi: 10.1016/j.exphem.2006.01.009.


Objective: Insulin-like growth factor (IGF)-binding proteins (IGFBPs) are a family of proteins thought to modulate IGF function. By employing an in vitro culture system of human hematopoietic stem cells cocultured with murine bone marrow stromal cells, we examined the effects of IGF-I and IGFBPs on early B-cell development.

Materials and methods: Human CD34(+) bone marrow cells were cocultured with murine stromal MS-5 cells for 4 weeks, and pro-B-cell number was analyzed by flow cytometry. After administration of reagents that are supposed to modulate IGF-I or IGFBP function to the culture, the effect on pro-B-cell development was examined.

Results: After cultivation for 4 weeks, effective induction of pro-B-cell proliferation was observed. Experiments using several distinct factors, all of which neutralize IGF-I function, revealed that impairment of IGF-I function results in a significant reduction in pro-B-cell development from CD34(+) cells. In addition, when the effect of recombinant proteins of IGFBPs and antibodies against IGFBPs were tested, IGFBP-3 was found to inhibit pro-B-cell development, while IGFBP-6 was required for pro-B-cell development.

Conclusions: IGF-I is essential for development of bone marrow CD34(+) cells into pro-B cells. Moreover, IGFBPs are likely involved in regulation of pro-B-cell development.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, CD34 / metabolism
  • B-Lymphocytes / cytology
  • B-Lymphocytes / physiology*
  • Cell Differentiation / drug effects*
  • Cell Differentiation / physiology
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Coculture Techniques
  • Flow Cytometry
  • Hematopoietic Stem Cells / cytology
  • Hematopoietic Stem Cells / physiology*
  • Humans
  • Insulin-Like Growth Factor Binding Proteins / metabolism
  • Insulin-Like Growth Factor Binding Proteins / pharmacology*
  • Insulin-Like Growth Factor I / metabolism
  • Insulin-Like Growth Factor I / pharmacology*
  • Mice
  • Stromal Cells / cytology
  • Stromal Cells / physiology


  • Antigens, CD34
  • Insulin-Like Growth Factor Binding Proteins
  • Insulin-Like Growth Factor I