Intraarticularly-Injected Mesenchymal Stem Cells Stimulate Anti-Inflammatory Molecules and Inhibit Pain Related Protein and Chondrolytic Enzymes in a Monoiodoacetate-Induced Rat Arthritis Model.

Toru Ichiseki,Ayumi Kaneuji,Masanobu Tsuchiya,Shusuke Ueda,Norio Kawahara,Yoshimichi Ueda,Daisuke Souma,Miyako Shimasaki

doi:10.3390/ijms19010203

Toru Ichiseki, Ayumi Kaneuji + Show 6 more

Open Access

https://doi.org/10.3390/ijms19010203

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Abstract

Persistent inflammation is well known to promote the progression of arthropathy. mesenchymal stem cells (MSCs) have been shown to possess anti-inflammatory properties and tissue differentiation potency. Although the experience so far with the intraarticular administration of mesenchymal stem cell (MSC) to induce cartilage regeneration has been disappointing, MSC implantation is now being attempted using various surgical techniques. Meanwhile, prevention of osteoarthritis (OA) progression and pain control remain important components of the treatment of early-stage OA. We prepared a shoulder arthritis model by injecting monoiodoacetate (MIA) into a rat shoulder, and then investigated the intraarticular administration of MSC from the aspects of the cartilage protective effect associated with their anti-inflammatory property and inhibitory effect on central sensitization of pain. When MIA was administered in this rat shoulder arthritis model, anti-Calcitonin Gene Related Peptide (CGRP) was expressed in the joint and C5 spinal dorsal horn. Moreover, expression of A disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTS5), a marker of joint cartilage injury, was similarly elevated following MIA administration. When MSC were injected intraarticularly after MIA, the expression of CGRP in the spinal dorsal horn was significantly deceased, indicating suppression of the central sensitization of pain. The expression of ADAMTS 5 in joint cartilage was also significantly inhibited by MSC administration. In contrast, a significant increase in the expression of TNF-α stimulated gene/protein 6 (TSG-6), an anti-inflammatory and cartilage protective factor shown to be produced and secreted by MSC intraarticularly, was found to extend to the cartilage tissue following MSC administration. In this way, the intraarticular injection of MSC inhibited the central sensitization of pain and increased the expression of the anti-inflammatory and cartilage protective factor TSG-6. As the least invasive conservative strategies possible are desirable in the actual clinical setting, the intraarticular administration of MSC, which appears to be effective for the treatment of pain and cartilage protection in early-stage arthritis, may achieve these aims.

Highlights

The joint cartilage degeneration, injury and pain typically associated with arthropathy markedly impair patient quality of life (QOL)
Since central sensitization of pain of shoulder joint origin can be investigated in the spinal dorsal horn of C5 [19,20], we studied Calcitonin Gene Related Peptide (CGRP) expression at C5
It could be confirmed that mesenchymal stem cells (MSCs) administration inhibited central sensitization (Figure 1)

Summary

Introduction

The joint cartilage degeneration, injury and pain typically associated with arthropathy markedly impair patient quality of life (QOL). When considering treatment for affected joints, interventions that both help to preserve the joints themselves and to control pain are required. When considering the treatment of arthropathy, in the same way as common therapeutic endpoints such as joint preservation and cartilage regeneration, it is important to keep in mind issues such as pain control and central sensitization of pain [8]. Numerous investigations using mesenchymal stem cell (MSC) have been undertaken aiming to regenerate joint cartilage degenerated and injured during the course of osteoarthritis and other joint pathologies [9,10]. The results of cartilage regeneration obtained with intraarticular administration of MSC alone have not been encouraging, and surgical techniques using scaffolds are being increasingly attempted [11,12,13]

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