Recruitment of stem and progenitor cells from the bone marrow niche requires MMP-9 mediated release of Kit-ligand

Beate Heissig, Koichi Hattori, Sergio Dias, Matthias Friedrich, Barbara Ferris, Neil R. Hackett, Ronald Crystal, Peter Besmer, David Lyden, Malcolm A.S. Moore, Zena Werb, Shahin Rafii

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1397 Citations (Scopus)

Abstract

Stem cells within the bone marrow (BM) exist in a quiescent state or are instructed to differentiate and mobilize to circulation following specific signals. Matrix metalloproteinase-9 (MMP-9), induced in BM cells, releases soluble Kit-ligand (sKitL), permitting the transfer of endothelial and hematopoietic stem cells (HSCs) from the quiescent to proliferative niche. BM ablation induces SDF-1, which upregulates MMP-9 expression, and causes shedding of sKitL and recruitment of c-Kit+ stem/progenitors. In MMP-9-/- mice, release of sKitL and HSC motility are impaired, resulting in failure of hematopoietic recovery and increased mortality, while exogenous sKitL restores hematopoiesis and survival after BM ablation. Release of sKitL by MMP-9 enables BM repopulating cells to translocate to a permissive vascular niche favoring differentiation and reconstitution of the stem/progenitor cell pool.

Original languageEnglish
Pages (from-to)625-637
Number of pages13
JournalCell
Volume109
Issue number5
DOIs
Publication statusPublished - 31 May 2002
Externally publishedYes

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ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Heissig, B., Hattori, K., Dias, S., Friedrich, M., Ferris, B., Hackett, N. R., Crystal, R., Besmer, P., Lyden, D., Moore, M. A. S., Werb, Z., & Rafii, S. (2002). Recruitment of stem and progenitor cells from the bone marrow niche requires MMP-9 mediated release of Kit-ligand. Cell, 109(5), 625-637. https://doi.org/10.1016/S0092-8674(02)00754-7