Cell mediated ECM-degradation as an emerging tool for anti-fibrotic strategy

Abstract

Investigation into the role of cells with respect to extracellular matrix (ECM) remodeling is still in its infancy. Particularly, ECM degradation is an indispensable process during the recovery from fibrosis. Cells with ECM degradation ability due to the secretion of various matrix metalloproteinases (MMPs) have emerged as novel contributors to the treatment of fibrotic diseases. In this review, we focus on the ECM degradation ability of cells associated with the repertoire of MMPs that facilitate the attenuation of fibrosis through the inhibition of ECM deposition. Besides, innovative approaches to engineering and characterizing cells with degradation ability, as well as elucidating the mechanism of the ECM degradation, are also illustrated. Studies conducted to date on the use of cell-based degradation for therapeutic purposes to combat fibrosis are summarized. Finally, we discuss the therapeutic potential of cells with high degradation ability, hoping to bridge the gap between benchside research and bedside applications in treating fibrotic diseases.

Exploring Extracellular Matrix Crosslinking as a Therapeutic Approach to Fibrosis

“…Delivery of ECM-degradation enzymes such as MMPs has been suggested and explored, but the approach can be limited by side effects, so more selective delivery approaches may be necessary [ 14 ]. Cellular therapy approaches based on cell types possessing ECM-modifying and restoration capacities, such as mesenchymal stem cells and fibrolytic macrophages, may offer an additional strategy [ 10 , 95 , 100 , 101 , 102 ]. How to target and normalize diseased ECM and restore healthy tissue structure and function may be the biggest challenge of this research field.…”

Exploring Extracellular Matrix Crosslinking as a Therapeutic Approach to Fibrosis

“…Delivery of ECM-degradation enzymes such as MMPs has been suggested and explored, but the approach can be limited by side effects, so more selective delivery approaches may be necessary [16]. Cellular therapy approaches based on cell types possessing ECM modifying and restoration capacities, such as mesenchymal stem cells and fibrolytic macrophages, may offer an additional strategy [10,95,[102][103][104]. How to target and normalize diseased ECM and restore healthy tissue structure and function may be the biggest challenge of this research field.…”

Extracellular matrix stiffness mediates insulin secretion in pancreatic islets via mechanosensitive Piezo1 channel regulated Ca2+ dynamics

“…In T2D, increased ECM deposition, specifically increases in type I and type III collagen, fibronectin, and hyaluronan lead to increases in tissue stiffness [10] , [14] . In PDAC, there is an imbalance between ECM synthesis and degradation resulting in excess type I and type III collagen deposition, which increases tissue stiffness and supports cancer cell survival and proliferation [9] , [15] , [16] , [17] , [18] . The progression from a healthy pancreas to PDAC highlights increased stiffness due to fibrosis, implying altered mechanotransduction pathways [19] .…”