Secretion of fibrinolytic enzymes facilitates human mesenchymal stem cell invasion into fibrin clots

Cells Tissues Organs. 2010;191(1):36-46. doi: 10.1159/000215579. Epub 2009 Apr 24.

Abstract

Adult human mesenchymal stem cells (hMSC) are involved in wound healing and regeneration of mesodermal tissue, but the underlying homing mechanisms are not well understood. Fibrin clot formation is associated with most wound healing processes and potentially guides the recruitment of hMSC. The objective of this study is the investigation of a fibrinolytic capacity, which is required for hMSC to migrate into a wounded tissue and thus to contribute to tissue regeneration. Using RT-PCR, semiquantitative real-time PCR and ELISA, we detected key components of the fibrinolytic cascade, including the urokinase plasminogen activator (uPA) and its receptor (uPAR), the tissue plasminogen activator (tPA) and the plasminogen activator inhibitor (PAI), suggesting a strong fibrinolytic activity of hMSC. To test this activity in a functional assay, we cultured fibrin-embedded hMSC in vitro for 7 days. The cells efficiently dissolved the surrounding fibrin mesh into the fibrin degradation products, the fibrinopeptides. The fibrinolytic activity of hMSC and human dermal fibroblasts, known to be critically involved in skin wound extracellular matrix remodeling, was similar. Our results suggest that a high intrinsic fibrinolytic capacity of hMSC mediates the invasion into a fibrin clot of a wounded tissue.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Cell Movement*
  • Cells, Cultured
  • Extracellular Matrix / metabolism
  • Fibrin / metabolism*
  • Fibrin Fibrinogen Degradation Products / metabolism
  • Fibrinolysis / physiology*
  • Fibroblasts / cytology
  • Fibroblasts / physiology
  • Humans
  • Mesenchymal Stem Cells / cytology
  • Mesenchymal Stem Cells / physiology*
  • Plasminogen Inactivators / genetics
  • Plasminogen Inactivators / metabolism
  • Receptors, Urokinase Plasminogen Activator / genetics
  • Receptors, Urokinase Plasminogen Activator / metabolism
  • Skin / cytology
  • Skin / injuries
  • Skin / physiopathology
  • Tissue Plasminogen Activator / genetics
  • Tissue Plasminogen Activator / metabolism
  • Urokinase-Type Plasminogen Activator / genetics
  • Urokinase-Type Plasminogen Activator / metabolism
  • Wound Healing

Substances

  • Fibrin Fibrinogen Degradation Products
  • Plasminogen Inactivators
  • Receptors, Urokinase Plasminogen Activator
  • Fibrin
  • Tissue Plasminogen Activator
  • Urokinase-Type Plasminogen Activator