The tissue inhibitor of metalloproteinases-1 improves migration and adhesion of 
hematopoietic stem and progenitor cells.

Wilk, C. M.; Schildberg, F. A.; Lauterbach, M.; Cadeddu, R.; Fröbel, J.; Westphal, V.; Tolba, R. H.; Hell, S. W.; Czibere, A.; Bruns, I.; Haas, R.

doi:10.1016/j.exphem.2013.04.010

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Journal Article

The tissue inhibitor of metalloproteinases-1 improves migration and adhesion of hematopoietic stem and progenitor cells.

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Lauterbach, M.
Department of NanoBiophotonics, MPI for biophysical chemistry, Max Planck Society;

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Westphal, V.
Department of NanoBiophotonics, MPI for biophysical chemistry, Max Planck Society;

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Hell, S. W.
Department of NanoBiophotonics, MPI for biophysical chemistry, Max Planck Society;

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Citation

Wilk, C. M., Schildberg, F. A., Lauterbach, M., Cadeddu, R., Fröbel, J., Westphal, V., et al. (2013). The tissue inhibitor of metalloproteinases-1 improves migration and adhesion of hematopoietic stem and progenitor cells. Experimental Hematology, 41(9), 823-831. doi:10.1016/j.exphem.2013.04.010.

Cite as: https://hdl.handle.net/11858/00-001M-0000-0014-5330-6

Abstract

Homing and engraftment of hematopoietic stem and progenitor cells (HSPCs) during bone marrow transplantation are critically dependent on integrins such as β1-integrin. In the present study, we show that β1-integrin and the tetraspanin CD63 form a cell surface receptor complex for the soluble serum protein tissue inhibitor of metalloproteinases-1 (TIMP-1) on human CD34+ HSPCs. Through binding to this receptor complex, TIMP-1 activates β1-integrin, increases adhesion and migration of human CD34+ cells, and protects these cells from induced apoptosis. TIMP-1 stimulation in murine bone marrow mononuclear cells also promotes migration and adhesion; this is associated with augmented homing of murine mononuclear cells and of murine LSK+ cells during bone marrow transplantation. These results not only indicate that TIMP-1 is conducive to HSPC homing; they also identify CD63 and β1-integrin as a TIMP-1 receptor complex on HSPCs.