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Open Access 01-10-2020 | Osteoarthrosis | Original Article

TissueGene-C promotes an anti-inflammatory micro-environment in a rat monoiodoacetate model of osteoarthritis via polarization of M2 macrophages leading to pain relief and structural improvement

Authors: Hyeonyoul Lee, Heungdeok Kim, Jinwon Seo, Kyoungbaek Choi, Yunsin Lee, Kiwon Park, Sujeong Kim, Ali Mobasheri, Heonsik Choi

Published in: Inflammopharmacology | Issue 5/2020

Abstract

Osteoarthritis (OA) is the most common form of arthritis, characterized by cartilage destruction, pain and inflammation in the joints. Existing medications can provide relief from the symptoms, but their effects on the progression of the disease are limited. TissueGene-C (TG-C) is a novel cell and gene therapy for the treatment of OA, comprising a mixture of human allogeneic chondrocytes and irradiated cells engineered to overexpress transforming growth factor-β1 (TGF-β1). This study aims to investigate the efficacy and mechanism of action of TG-C in a rat model of OA. Using the monosodium-iodoacetate (MIA) model of OA, we examined whether TG-C could improve OA symptoms and cartilage structure in rats. Our results showed that TG-C provided pain relief and cartilage structural improvement in the MIA OA model over 56 days. In parallel with these long-term effects, cytokine profiles obtained on day 4 revealed increased expression of interleukin-10 (IL-10), an anti-inflammatory cytokine, in the synovial lavage fluid. Moreover, the increased levels of TGF-β1 and IL-10 caused by TG-C induced the expression of arginase 1, a marker of M2 macrophages, and decreased the expression of CD86, a marker of M1 macrophages. These results suggest that TG-C exerts a beneficial effect on OA by inducing a M2 macrophage-dominant micro-environment. Cell therapy using TG-C may be a promising strategy for targeting the underlying pathogenic mechanisms of OA, reducing pain, improving function, and creating a pro-anabolic micro-environment. This environment supports cartilage structure regeneration and is worthy of further evaluation in future clinical trials.

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Title: TissueGene-C promotes an anti-inflammatory micro-environment in a rat monoiodoacetate model of osteoarthritis via polarization of M2 macrophages leading to pain relief and structural improvement
Authors: Hyeonyoul Lee
Heungdeok Kim
Jinwon Seo
Kyoungbaek Choi
Yunsin Lee
Kiwon Park
Sujeong Kim
Ali Mobasheri
Heonsik Choi
Publication date: 01-10-2020
Publisher: Springer International Publishing
Keywords: Osteoarthrosis
Osteoarthrosis
Gene Therapy in Oncology
Published in: Inflammopharmacology / Issue 5/2020
Print ISSN: 0925-4692
Electronic ISSN: 1568-5608
DOI: https://doi.org/10.1007/s10787-020-00738-y

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TissueGene-C promotes an anti-inflammatory micro-environment in a rat monoiodoacetate model of osteoarthritis via polarization of M2 macrophages leading to pain relief and structural improvement

Abstract

At a glance: The ONWARDS insulin icodec trials

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Abstract

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