Chemokine-mobilized adult stem cells; defining a better hematopoietic graft

Leukemia. 2008 Mar;22(3):466-73. doi: 10.1038/sj.leu.2405021. Epub 2007 Nov 1.

Abstract

Stem cell research is currently focused on totipotent stem cells and their therapeutic potential, however adult stem cells, while restricted to differentiation within their tissue or origin, also have therapeutic utility. Transplantation with bone marrow hematopoietic stem cells (HSC) has been used for curative therapy for decades. More recently, alternative sources of HSC, particularly those induced to exit marrow or mobilize to peripheral blood by G-CSF, have become the most widely used hematopoietic graft and show significant superiority to marrow HSC. The chemokine/chemokine receptor axis also mobilizes HSC that occurs more rapidly than with G-CSF. In mice, the HSC and progenitor cells (HPC) mobilized by the CXCR2 receptor agonist GRObeta can be harvested within minutes of administration and show significantly lower levels of apoptosis, enhanced homing to marrow, expression of more activated integrin receptors and superior repopulation kinetics and more competitive engraftment than the equivalent cells mobilized by G-CSF. These characteristics suggest that chemokine axis-mobilized HSC represent a population of adult stem cells distinct from those mobilized by G-CSF, with superior therapeutic potential. It remains to be determined if the chemokine mobilization axis can be harnessed to mobilize other populations of unique adult stem cells with clinical utility.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Adult Stem Cells / classification
  • Adult Stem Cells / cytology
  • Adult Stem Cells / drug effects*
  • Animals
  • Chemokine CXCL12 / physiology
  • Chemokine CXCL2 / pharmacology
  • Chemokines / pharmacology*
  • Granulocyte Colony-Stimulating Factor / pharmacology
  • Hematopoietic Stem Cell Mobilization / methods*
  • Hematopoietic Stem Cell Transplantation
  • Hematopoietic Stem Cells / classification
  • Hematopoietic Stem Cells / cytology
  • Hematopoietic Stem Cells / drug effects*
  • Humans
  • Immunophenotyping
  • Mice
  • Mice, Congenic
  • Mice, Inbred C57BL
  • Peripheral Blood Stem Cell Transplantation
  • Radiation Chimera
  • Receptors, Chemokine / agonists*
  • Receptors, Chemokine / physiology
  • Receptors, Interleukin-8B / agonists
  • Receptors, Interleukin-8B / drug effects

Substances

  • Chemokine CXCL12
  • Chemokine CXCL2
  • Chemokines
  • Receptors, Chemokine
  • Receptors, Interleukin-8B
  • Granulocyte Colony-Stimulating Factor