Hematopoietic progenitor cell mobilization by granulocyte colony-stimulating factor and erythropoietin in the absence of matrix metalloproteinase-9

Simon N. Robinson, S. M. Seina, J. C. Gohr, John G Sharp

Research output: Contribution to journalArticle

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Abstract

The use of mobilized hematopoietic progenitor cells (HPC) has largely replaced the use of bone marrow HPC for autologous and allogeneic transplantation; however, the mechanisms of HPC mobilization remain unclear. A better understanding of these mechanisms, may allow the development of improved (potentially more rapid and/or higher yield) HPC mobilization strategies, especially for patients who mobilize poorly using current mobilization protocols. Clinically, granulocyte colony-stimulating factor (G-CSF) is widely used to induce HPC mobilization, and evidence suggests that metalloproteinase enzymes released by activated granulocytes play an important role in the G-CSF-induced HPC mobilization. These enzymes may act to disrupt putative cell-cell and/or cell-extracellular matrix interactions within the hematopoietic microenvironment thereby releasing HPC into the blood. Matrix metalloproteinase-9 (MMP-9) appears to be important for G-CSF-induced mobilization. Using an MMP-9 knock-out (KO) mouse model, we investigated the role of MMP-9 in G-CSF and erythropoietin (EPO)-based HPC mobilization at clinically relevant cytokine doses. There were few hematologic or hematopoietic differences between the wild-type and MMP-9KO mice during steady-state hematopoiesis. When treated subcutaneously with EPO (500 U/kg per day) and G-CSF (15 μg/kg per day) for 5 days and assayed on day 6, similarly increased extramedullary hematopoiesis and numbers of HPC in the spleen and blood were observed for both the wild-type and MMP-9KO mice. These data demonstrate that MMP-9 is not required for EPO + G-CSF mobilization and that alternative mobilization mechanisms must be active at clinically relevant cytokine concentrations.

Original languageEnglish (US)
Pages (from-to)317-328
Number of pages12
JournalStem Cells and Development
Volume14
Issue number3
DOIs
StatePublished - Jun 1 2005

Fingerprint

Matrix Metalloproteinase 9
Granulocyte Colony-Stimulating Factor
Erythropoietin
Hematopoietic Stem Cells
Matrix Metalloproteinases
Extramedullary Hematopoiesis
Cytokines
Autologous Transplantation
Cell Transplantation
Homologous Transplantation
Hematopoiesis
Metalloproteases
Enzymes
Granulocytes
Knockout Mice
Extracellular Matrix
Spleen
Bone Marrow

ASJC Scopus subject areas

  • Hematology

Cite this

Hematopoietic progenitor cell mobilization by granulocyte colony-stimulating factor and erythropoietin in the absence of matrix metalloproteinase-9. / Robinson, Simon N.; Seina, S. M.; Gohr, J. C.; Sharp, John G.

In: Stem Cells and Development, Vol. 14, No. 3, 01.06.2005, p. 317-328.

Research output: Contribution to journalArticle

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