Tissue regeneration during wound healing or

cancer growth and progression depends on the establishment

of a cellular microenvironment. Mesenchymal stem

cells (MSC) are part of this cellular microenvironment,

where they functionally modulate cell homing, angiogenesis,

and immune modulation. MSC recruitment involves

detachment of these cells from their niche, and finally MSC

migration into their preferred niches; the wounded area, the

tumor bed, and the BM, just to name a few. During this

recruitment phase, focal proteolysis disrupts the extracellular

matrix (ECM) architecture, breaks cell–matrix

interactions with receptors, and integrins, and causes the

release of bioactive fragments from ECM molecules. MSC

produce a broad array of proteases, promoting remodeling

of the surrounding ECM through proteolytic mechanisms.

The fibrinolytic system, with its main player plasmin, plays

a crucial role in cell migration, growth factor bioavailability,

and the regulation of other protease systems during

inflammation, tissue regeneration, and cancer. Key components

of the fibrinolytic cascade, including the urokinase

plasminogen activator receptor (uPAR) and plasminogen

activator inhibitor-1 (PAI-1), are expressed in MSC. This

review will introduce general functional properties of the

fibrinolytic system, which go beyond its known function of

fibrin clot dissolution (fibrinolysis). We will focus on the

role of the fibrinolytic system for MSC biology, summarizing

our current understanding of the role of the

fibrinolytic system for MSC recruitment and the functional

consequences for tissue regeneration and cancer. Aspects

of MSC origin, maintenance, and the mechanisms by

which these cells contribute to altered protease activity in

the microenvironment under normal and pathological

conditions will also be discussed.

Title

Cellular and Molecular Life Sciences

Publisher

SPRINGER

Publisher Country

United States of America

Publication Type

Prtinted only

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Year

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