Protective Effects of a Hyaluronan-Binding Peptide (P15-1) on Mesenchymal Stem Cells in an Inflammatory Environment.

Thorsten Kirsch,Olivia Braender-Carr,Fenglin Zhang,Mary K Cowman

doi:10.3390/ijms22137058

Thorsten Kirsch, Olivia Braender-Carr + Show 2 more

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https://doi.org/10.3390/ijms22137058

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Abstract

Mesenchymal stem cells (MSCs) obtained from various sources, including bone marrow, have been proposed as a therapeutic strategy for the improvement of tissue repair/regeneration, including the repair of cartilage defects or lesions. Often the highly inflammatory environment after injury or during diseases, however, greatly diminishes the therapeutic and reparative effectiveness of MSCs. Therefore, the identification of novel factors that can protect MSCs against an inflammatory environment may enhance the effectiveness of these cells in repairing tissues, such as articular cartilage. In this study, we investigated whether a peptide (P15-1) that binds to hyaluronan (HA), a major component of the extracellular matrix of cartilage, protects bone-marrow-derived MSCs (BMSCs) in an inflammatory environment. The results showed that P15-1 reduced the mRNA levels of catabolic and inflammatory markers in interleukin-1beta (IL-1β)-treated human BMSCs. In addition, P15-1 enhanced the attachment of BMSCs to HA-coated tissue culture dishes and stimulated the chondrogenic differentiation of the multipotential murine C3H/10T1/2 MSC line in a micromass culture. In conclusion, our findings suggest that P15-1 may increase the capacity of BMSCs to repair cartilage via the protection of these cells in an inflammatory environment and the stimulation of their attachment to an HA-containing matrix and chondrogenic differentiation.

Highlights

Mesenchymal stem cells (MSCs), including bone-marrow-derived mesenchymal stem cells (BMSCs), are essential for the repair of many tissues, including the repair of cartilage defects or lesions
Previous studies have shown that an inflammatory environment inhibits chondrogenic differentiation of BMSCs [9,10]
We showed that IL1β, one of the main inflammatory cytokines in the osteoarthritic or injured joint [50], stimulates the expression of catabolic markers, Cox-2 and IL-6, and MMP-3 and MMP-13, in human BMSCs

Summary

Introduction

Mesenchymal stem cells (MSCs), including bone-marrow-derived mesenchymal stem cells (BMSCs), are essential for the repair of many tissues, including the repair of cartilage defects or lesions. MSCs have been shown to exhibit anti-inflammatory properties. The use of MSCs in various diseases and tissue repair/regeneration is a matter of intensive research [1,2,3,4]. The MSC transplantation in chronic wounds has been suggested. Studies showed low success of improved wound healing after injection of adipose-derived MSCs and/or BMSCs, most likely due to the harsh injury microenvironment that is infiltrated by inflammatory and catabolic cytokines and reactive oxygen species [5,6,7]. Previous studies have shown that prolonged exposure of MSCs to interleukin (IL)-1β, the main cytokine present in the injured or osteoarthritic joints, results in an inhibition of chondrogenic differentiation and increased expression of matrix-degrading enzymes by MSCs [8,9,10]

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