Enhancement of Anti-Inflammatory and Osteogenic Abilities of Mesenchymal Stem Cells via Cell-to-Cell Adhesion to Periodontal Ligament-Derived Fibroblasts.

Keita Suzuki,Akira Ishisaki,Shunsuke Sawada,Naoki Takizawa,Naoyuki Chosa,Takashi Yaegashi

doi:10.1155/2017/3296498

Keita Suzuki, Akira Ishisaki + Show 4 more

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https://doi.org/10.1155/2017/3296498

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Abstract

Mesenchymal stem cells (MSCs) are involved in anti-inflammatory events and tissue repair; these functions are activated by their migration or homing to inflammatory tissues in response to various chemokines. However, the mechanism by which MSCs interact with other cell types in inflammatory tissue remains unclear. We investigated the role of periodontal ligament fibroblasts (PDL-Fs) in regulating the anti-inflammatory and osteogenic abilities of bone marrow-derived- (BM-) MSCs. The expression of monocyte chemotactic protein- (MCP-)1 was significantly enhanced by stimulation of PDL-Fs with inflammatory cytokines. MCP-1 induced the migratory ability of BM-MSCs but not PDL-Fs. Expression levels of anti-inflammatory and inflammatory cytokines were increased and decreased, respectively, by direct-contact coculture between MSCs and PDL-Fs. In addition, the direct-contact coculture enhanced the expression of MSC markers that play important roles in the self-renewal and maintenance of multipotency of MSCs, which in turn induced the osteogenic ability of the cells. These results suggest that MCP-1 induces the migration and homing of BM-MSCs into the PDL inflammatory tissue. The subsequent adherence of MSCs to PDL-Fs plays an immunomodulatory role to terminate inflammation during wound healing and upregulates the expression stem cell markers to enhance the stemness of MSCs, thereby facilitating bone formation in damaged PDL tissue.

Highlights

Mesenchymal stem cells (MSCs) are adult stem cells with the ability to differentiate into mesenchymal cells such as osteoblasts, adipocytes, chondrocytes, and fibroblasts, while retaining self-renewal and migration abilities [1]
We examined the expression of monocyte chemotactic protein- (MCP-)1 in periodontal ligament fibroblasts (PDL-Fs) stimulated with the inflammatory cytokines interleukin (IL)-1β, IL-6/soluble IL-6 receptor, or tumor necrosis factor (TNF)-α, and its effect on the recruitment of MSCs into periodontal ligament (PDL) inflammatory tissues in vivo
These results indicated that inflammatory cytokines enhanced the production of MCP-1 in PDL-Fs

Summary

Introduction

Mesenchymal stem cells (MSCs) are adult stem cells with the ability to differentiate into mesenchymal cells such as osteoblasts, adipocytes, chondrocytes, and fibroblasts, while retaining self-renewal and migration abilities [1]. Upon activation by tissue damage in vivo, MSCs contribute to tissue repair through a multitude of processes such as self-renewal, migration, and differentiation. Stem cell therapy relies on the appropriate homing and engraftment capacity of stem cells. Chemokines such as monocyte chemotactic protein (MCP-1/CCL2) and/or stromal cell-derived factor-1 (SDF1/CXCL12) and their receptors such as CCR2 and CXCR4 promote the effective homing of MSCs. The CXCR4 ligand SDF-1 has a dose-dependent effect on human and murine bone marrow-derived MSC (BM-MSC) migration [17,18,19]. Kanbe et al [20] demonstrated that synovial fibroblasts secrete high levels of SDF-1 in osteoarthritis and rheumatoid

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