University of Oulu

Lee, H., Kim, H., Seo, J. et al. 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. Inflammopharmacol 28, 1237–1252 (2020). https://doi.org/10.1007/s10787-020-00738-y

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

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Author: Lee, Hyeonyoul1; Kim, Heungdeok1; Seo, Jinwon1;
Organizations: 1Institute of Bio Innovation Research, Kolon Life Science, Inc., Magok-dong, Gangseo-gu, Seoul, Korea
2Department of Regenerative Medicine, State Research Institute Center for Innovative Medicine, Santariskiu 5, 08406, Vilnius, Lithuania
3Research Unit of Medical Imaging, Physics and Technology, Faculty of Medicine, University of Oulu, 90014, Oulu, Finland
4Department of Orthopedics and Department of Rheumatology and Clinical Immunology, University Medical Center Utrecht, 508 GA, Utrecht, The Netherlands
5Centre for Sport, Exercise and Osteoarthritis Research Versus Arthritis, Queen’s Medical Centre, Nottingham, NG7 2UH, UK
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 5.6 MB)
Persistent link: http://urn.fi/urn:nbn:fi-fe2020102988770
Language: English
Published: Springer Nature, 2020
Publish Date: 2020-10-29
Description:

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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Series: Inflammopharmacology
ISSN: 0925-4692
ISSN-E: 1568-5608
ISSN-L: 0925-4692
Volume: 28
Issue: 5
Pages: 1237 - 1252
DOI: 10.1007/s10787-020-00738-y
OADOI: https://oadoi.org/10.1007/s10787-020-00738-y
Type of Publication: A1 Journal article – refereed
Field of Science: 3111 Biomedicine
Subjects:
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