Effects of matrix metalloproteinases on the fate of mesenchymal stem cells

Stem Cell Res Ther. 2016 Sep 9;7(1):129. doi: 10.1186/s13287-016-0393-1.


Mesenchymal stem cells (MSCs) have great potential as a source of cells for cell-based therapy because of their ability for self-renewal and differentiation into functional cells. Moreover, matrix metalloproteinases (MMPs) have a critical role in the differentiation of MSCs into different lineages. MSCs also interact with exogenous MMPs at their surface, and regulate the pericellular localization of MMP activities. The fate of MSCs is regulated by specific MMPs associated with a key cell lineage. Recent reports suggest the integration of MMPs in the differentiation, angiogenesis, proliferation, and migration of MSCs. These interactions are not fully understood and warrant further investigation, especially for their application as therapeutic tools to treat different diseases. Therefore, overexpression of a single MMP or tissue-specific inhibitor of metalloproteinase in MSCs may promote transdifferentiation into a specific cell lineage, which can be used for the treatment of some diseases. In this review, we critically discuss the identification of various MMPs and the signaling pathways that affect the differentiation, migration, angiogenesis, and proliferation of MSCs.

Keywords: Adipogenic differentiation; Angiogenesis; Chondrogenic differentiation; Extracellular matrix; Matrix metalloproteinases; Mesenchymal stem cells; Migration; Osteogenic differentiation; Proliferation.

Publication types

  • Review

MeSH terms

  • Animals
  • Cell Differentiation / physiology
  • Cell Lineage / physiology
  • Cell Transdifferentiation / physiology
  • Cell- and Tissue-Based Therapy / methods
  • Humans
  • Matrix Metalloproteinases / metabolism*
  • Mesenchymal Stem Cells / metabolism*
  • Signal Transduction / physiology
  • Stem Cells / metabolism*


  • Matrix Metalloproteinases