In vivo cellular imaging pinpoints the role of reactive oxygen species in the early steps of adult hematopoietic reconstitution

Blood. 2010 Jan 21;115(3):443-52. doi: 10.1182/blood-2009-05-222711. Epub 2009 Oct 1.

Abstract

Few techniques are available to characterize in vivo the early cellular dynamics of long-term reconstitution of hematopoiesis after transplantation of hematopoietic stem cells (HSCs) after lethal irradiation. Using a fiber-optic imaging system, we track the early steps of in vivo recruitment and proliferation of Lin(-)Sca-1(+)c-Kit(+)CD34(-) (LSKCD34(-)) HSCs highly enriched in HSCs and transplanted into lethally irradiated mice. Recruitment of the transplanted LSKCD34(-) hematopoietic cells first occurs in the femoral head and is continuous during 24 hours. Quantification of the fluorescence emitted by the transplanted hematopoietic cells shows that proliferation of LSKCD34(-) hematopoietic cells in the femoral head was potent 3 days after transplantation. Using a development of this fiber-optic imaging system, we show that the transplanted LSKCD34(-) hematopoietic cells are associated with vascularized structures as early as 5 hours after transplantation. This early association is dependent on reactive oxygen species (ROS) partly through the regulation of vascular cell adhesion molecule-1 expression on endothelial cells and is followed by a ROS-dependent proliferation of LSKCD34(-) hematopoietic cells. This new in vivo imaging technique permits the observation of the early steps of hematopoietic reconstitution by HSCs in long bones and shows a new role of ROS in the recruitment of HSCs by bone marrow endothelial cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, CD34 / metabolism
  • Antigens, Ly / metabolism
  • Cell Differentiation / drug effects
  • Cell Differentiation / physiology
  • Cell Movement / physiology
  • Cell Proliferation / drug effects
  • Femur / cytology
  • Femur / metabolism
  • Femur / physiology
  • Fiber Optic Technology / methods
  • Hematopoiesis / drug effects*
  • Hematopoiesis / physiology
  • Hematopoietic Stem Cell Transplantation
  • Hematopoietic Stem Cells / drug effects
  • Hematopoietic Stem Cells / metabolism
  • Hematopoietic Stem Cells / physiology
  • Membrane Proteins / metabolism
  • Mice
  • Mice, Transgenic
  • Models, Biological
  • Molecular Imaging / methods*
  • Proto-Oncogene Proteins c-kit / metabolism
  • Reactive Oxygen Species / metabolism
  • Reactive Oxygen Species / pharmacology*
  • Validation Studies as Topic
  • Whole-Body Irradiation

Substances

  • Antigens, CD34
  • Antigens, Ly
  • Ly6a protein, mouse
  • Membrane Proteins
  • Reactive Oxygen Species
  • Proto-Oncogene Proteins c-kit