Rapid Mobilization Reveals a Highly Engraftable Hematopoietic Stem Cell

Jonathan Hoggatt, Pratibha Singh, Tiffany A. Tate, Bin Kuan Chou, Shruti R. Datari, Seiji Fukuda, Liqiong Liu, Peter V. Kharchenko, Amir Schajnovitz, Ninib Baryawno, Francois E. Mercier, Joseph Boyer, Jason Gardner, Dwight M. Morrow, David T. Scadden, Louis M. Pelus

Research output: Contribution to journalArticle

27 Scopus citations

Abstract

Hematopoietic stem cell transplantation is a potential curative therapy for malignant and nonmalignant diseases. Improving the efficiency of stem cell collection and the quality of the cells acquired can broaden the donor pool and improve patient outcomes. We developed a rapid stem cell mobilization regimen utilizing a unique CXCR2 agonist, GROβ and the CXCR4 antagonist AMD3100. A single injection of both agents resulted in stem cell mobilization peaking within 15 min that was equivalent in magnitude to a standard multi-day regimen of granulocyte colony-stimulating factor (G-CSF). Mechanistic studies determined that rapid mobilization results from synergistic signaling on neutrophils, resulting in enhanced MMP-9 release, and unexpectedly revealed genetic polymorphisms in MMP-9 that alter activity. This mobilization regimen results in preferential trafficking of stem cells that demonstrate a higher engraftment efficiency than those mobilized by G-CSF. Our studies suggest a potential new strategy for the rapid collection of an improved hematopoietic graft. A new strategy for stem cell mobilization enables rapid collection of an improved hematopoietic graft in humans.

Original languageEnglish (US)
Pages (from-to)191-204.e10
JournalCell
Volume172
Issue number1-2
DOIs
StatePublished - Jan 11 2018

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Keywords

  • AMD3100
  • CXCR2
  • CXCR4
  • MMP-9
  • bone marrow transplantation
  • granulocyte colony-stimulating factor
  • hematopoiesis
  • hematopoietic stem cell mobilization
  • neutrophils
  • stem cell trafficking

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Hoggatt, J., Singh, P., Tate, T. A., Chou, B. K., Datari, S. R., Fukuda, S., Liu, L., Kharchenko, P. V., Schajnovitz, A., Baryawno, N., Mercier, F. E., Boyer, J., Gardner, J., Morrow, D. M., Scadden, D. T., & Pelus, L. M. (2018). Rapid Mobilization Reveals a Highly Engraftable Hematopoietic Stem Cell. Cell, 172(1-2), 191-204.e10. https://doi.org/10.1016/j.cell.2017.11.003