Bone marrow mesenchymal stem cells can be mobilized into peripheral blood by G-CSF in vivo and integrate into traumatically injured cerebral tissue

Neurol Sci. 2011 Aug;32(4):641-51. doi: 10.1007/s10072-011-0608-2. Epub 2011 Jun 16.

Abstract

The efficacy of granulocyte colony-stimulating factor (G-CSF) in mobilizing mesenchymal stem cells (MSCs) into peripheral blood (PB) and the ability of PB-MSCs incorporated into injured brain were tested. Colony forming, cell phenotype and differentiation potential of mouse MSCs mobilized by G-CSF (40 μg/kg) were evaluated. Mortality and pathological changes in mice with serious craniocerebral trauma plus G-CSF treatment (40 μg/kg) were investigated. Bone marrow (BM) cells derived from GFP mice were fractionated into MSCs, hematopoietic stem cells (HSCs), and non-MSC/HSCs using magnetic beads and adherent culture. The resultant cell populations were transplanted into injured mice. The in vivo integration and differentiation of the transplanted cells were detected immunocytochemically. The expression of SDF-1 in injured area of brain was tested by Western blot. G-CSF was able to mobilize MSCs into PB (fourfold increase). PB-MSCs possessed similar characteristics as BM-MSCs in terms of colony formation, the expression pattern of CD73, 44, 90, 106, 31 and 45, and multipotential of differentiation. Accumulative total mice mortality was lower in TG group (5/14) than that in T group (7/14). It was MSCs, not HSCs or non-MSC/HSC cells integrated into the damaged cerebral tissue and differentiated into cells expressing neural markers. Increased SDF-1 expression in injured area of brain was confirmed, which could facilitate the homing of MSCs to brain. G-CSF can mobilize MSCs into PB and MSCs in PB can integrate into injured cerebral tissue and transdifferentiated into neural cells and may benefit the repair of trauma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Western
  • Bone Marrow Cells / drug effects*
  • Brain / cytology*
  • Brain Injuries / therapy*
  • Cell Differentiation / drug effects
  • Chemokine CXCL12 / biosynthesis
  • Chemokine CXCL12 / genetics
  • Female
  • Flow Cytometry
  • Fluorescent Antibody Technique
  • Granulocyte Colony-Stimulating Factor / pharmacology*
  • Green Fluorescent Proteins
  • Male
  • Membrane Proteins / metabolism
  • Mesenchymal Stem Cell Transplantation / methods*
  • Mesenchymal Stem Cells / drug effects*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Recombinant Proteins
  • Wound Healing

Substances

  • Chemokine CXCL12
  • Cxcl12 protein, mouse
  • Membrane Proteins
  • Recombinant Proteins
  • Granulocyte Colony-Stimulating Factor
  • Green Fluorescent Proteins