Soluble factor cross-talk between human bone marrow-derived hematopoietic and mesenchymal cells enhances in vitro CFU-F and CFU-O growth and reveals heterogeneity in the mesenchymal progenitor cell compartment

Blood. 2005 Nov 1;106(9):3012-9. doi: 10.1182/blood-2005-01-0433. Epub 2005 Jul 19.


The homeostatic adult bone marrow (BM) is a complex tissue wherein physical and biochemical interactions serve to maintain a balance between the hematopoietic and nonhematopoietic compartments. To focus on soluble factor interactions occurring between mesenchymal and hematopoietic cells, a serum-free adhesion-independent culture system was developed that allows manipulation of the growth of both mesenchymal and hematopoietic human BM-derived progenitors and the balance between these compartments. Factorial experiments demonstrated a role for stem cell factor (SCF) and interleukin 3 (IL-3) in the concomitant growth of hematopoietic (CD45+) and nonhematopoietic (CD45-) cells, as well as their derivatives. Kinetic tracking of IL-3alpha receptor (CD123) and SCF receptor (CD117) expression on a sorted CD45- cell population revealed the emergence of CD45-CD123+ cells capable of osteogenesis. Of the total fibroblast colony-forming units (CFU-Fs) and osteoblast colony-forming units (CFU-O), approximately 24% of CFU-Fs and about 22% of CFU-Os were recovered from this population. Cell-sorting experiments demonstrated that the CD45+ cell population secreted soluble factors that positively affect the survival and proliferation of CFU-Fs and CFU-Os generated from the CD45- cells. Together, our results provide insight into the intercellular cytokine network between hematopoietic and mesenchymal cells and provide a strategy to mutually culture both mesenchymal and hematopoietic cells in a defined scalable bioprocess.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Differentiation
  • Cell Lineage
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Colony-Forming Units Assay
  • Culture Media, Serum-Free
  • Fibroblasts
  • Hematopoietic Stem Cells / cytology*
  • Hematopoietic Stem Cells / metabolism
  • Humans
  • Interleukin-3 / pharmacology
  • Interleukin-3 Receptor alpha Subunit
  • Leukocyte Common Antigens / metabolism
  • Mesenchymal Stem Cells / cytology*
  • Mesenchymal Stem Cells / metabolism
  • Osteoblasts / cytology*
  • Receptors, Interleukin-3 / metabolism
  • Stem Cell Factor / pharmacology


  • Culture Media, Serum-Free
  • IL3RA protein, human
  • Interleukin-3
  • Interleukin-3 Receptor alpha Subunit
  • Receptors, Interleukin-3
  • Stem Cell Factor
  • Leukocyte Common Antigens