Blood Journal
Leading the way in experimental and clinical research in hematology

MT1-MMP controls human mesenchymal stem cell trafficking and differentiation

  1. Changlian Lu1,2,
  2. Xiao-Yan Li2,
  3. Yuexian Hu2,
  4. R. Grant Rowe2, and
  5. Stephen J. Weiss2
  1. 1College of Pharmacy, Harbin Medical University, Harbin, China; and
  2. 2Division of Molecular Medicine and Genetics, Department of Internal Medicine, Life Sciences Institute, University of Michigan, Ann Arbor


Human mesenchymal stem cells (hMSCs) localized to bone marrow, nonhematopoietic organs, as well as perivascular niches are postulated to traffic through type I collagen-rich stromal tissues to first infiltrate sites of tissue damage, inflammation, or neoplasia and then differentiate. Nevertheless, the molecular mechanisms supporting the ability of hMSCs to remodel 3-dimensional (3D) collagenous barriers during trafficking or differentiation remain undefined. Herein, we demonstrate that hMSCs degrade and penetrate type I collagen networks in tandem with the expression of a 5-member set of collagenolytic matrix metalloproteinases (MMPs). Specific silencing of each of these proteases reveals that only a single membrane-tethered metalloenzyme, termed MT1-MMP, plays a required role in hMSC-mediated collagenolysis, 3D invasion, and intravasation. Further, once confined within type I collagen-rich tissue, MT1-MMP also controls hMSC differentiation in a 3D-specific fashion. Together, these data demonstrate that hMSC invasion and differentiation programs fall under the control of the pericellular collagenase, MT1-MMP.

  • Submitted June 17, 2009.
  • Accepted October 13, 2009.
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