title: Functional potentials of human hematopoietic progenitor cells are maintained by mesenchymal stromal cells and not impaired by plerixafor.
abstract: OBJECTIVE
  Mesenchymal stromal cells (MSCs) resemble an essential component of the bone marrow niche for maintenance of stemness of hematopoietic progenitor cells (HPCs). Perturbation of the C-X-C chemokine receptor type 4 (CXCR4)/stromal cell-derived factor-1α (SDF-1α) axis by plerixafor (AMD3100) mobilizes HPCs from their niche; however, little is known about how plerixafor affects interaction of HPCs and MSCs in vitro.
  
  
  METHODS
  We monitored cell division kinetics, surface expression of CD34 and CXCR4, migration behavior and colony-forming frequency of HPCs on co-culture with MSCs either with or without exposure to plerixafor.
  
  
  RESULTS
  Co-culture with MSCs significantly accelerated cell division kinetics of HPCs. Despite this, the proportion of CD34⁺ cells was significantly increased on co-culture, whereas the expression of CXCR4 was reduced. In addition, co-culture with MSCs led to significantly higher colony-forming capacity and enhanced migration rate of HPCs compared with mono-culture conditions. The composition of MSC sub-populations-and conversely their hematopoiesis supportive functions-may be influenced by culture conditions. We compared the stromal function of MSCs isolated with three different culture media. Overall, the supporting potentials of these MSC preparations were quite similar. Perturbation by the CXCR4-antagonist plerixafor reduced the cell division kinetics of HPCs on co-culture with MSCs. However, the progenitor cell potential of the HPCs as reflected by colony-forming capacity was not affected by plerixafor.
  
  
  CONCLUSIONS
  These results support the notion that the CXCR4/SDF-1α axis is critical for HPC-MSC interaction with regard to migration, adhesion and regulation of proliferation but not for maintenance of primitive progenitor cells.
authors.affiliation: Department of Medicine V, Heidelberg University, Heidelberg, Germany.
authors.forename: Annette
authors.initials: A
authors.lastname: Ludwig
authors.affiliation: Department of Medicine V, Heidelberg University, Heidelberg, Germany.
authors.forename: Rainer
authors.initials: R
authors.lastname: Saffrich
authors.affiliation: Department of Medicine V, Heidelberg University, Heidelberg, Germany.
authors.forename: Volker
authors.initials: V
authors.lastname: Eckstein
authors.affiliation: Institute of Medical Biometry, Heidelberg University, Heidelberg, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Bruckner
authors.affiliation: Helmholtz Institute for Biomedical Technology, Stem Cell Biology and Cellular Engineering, University of Aachen Medical School, Aachen, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Wagner
authors.affiliation: Department of Medicine V, Heidelberg University, Heidelberg, Germany.
authors.forename: Anthony D
authors.initials: AD
authors.lastname: Ho
authors.affiliation: Department of Medicine V, Heidelberg University, Heidelberg, Germany. Electronic address: patrick.wuchter@med.uni-heidelberg.de.
authors.forename: Patrick
authors.initials: P
authors.lastname: Wuchter
mesh_terms: D018952:Antigens, CD34 / Q000096:biosynthesis; D001596:Benzylamines; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects; D002448:Cell Adhesion / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D054377:Chemokine CXCL12 / Q000096:biosynthesis; D000080027:Cyclams; D005786:Gene Expression Regulation / Q000187:drug effects; D006410:Hematopoiesis / Q000187:drug effects; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000187:drug effects; D006571:Heterocyclic Compounds / Q000008:administration & dosage*; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects*; D019718:Receptors, CXCR4 / Q000037:antagonists & inhibitors / Q000096:biosynthesis
chemical_list: D018952:Antigens, CD34; D001596:Benzylamines; C527276:CXCR4 protein, human; D054377:Chemokine CXCL12; D000080027:Cyclams; D006571:Heterocyclic Compounds; D019718:Receptors, CXCR4; C088327:plerixafor
keywords: CXCR4/SDF-1α; hematopoietic progenitor cells; mesenchymal stromal cells; plerixafor; stem cell niche