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Soluble IL-6R promotes chondrogenic differentiation of mesenchymal stem cells to enhance the repair of articular cartilage defects using a rat model for rheumatoid arthritis
K. Yamagata1, S. Nakayamada2, T. Zhang3, X. Zhang4, Y. Tanaka5
- The First Department of Internal Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan.
- The First Department of Internal Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan.
- The First Department of Internal Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan.
- Research Center, The Fourth Hospital of Hebei Medical University and The Tumor Hospital of Hebei Province, Shijiazhuang, China.
- The First Department of Internal Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan. tanaka@med.uoeh-u.ac.jp
CER12438
2020 Vol.38, N°4
PI 0670, PF 0679
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PMID: 31694744 [PubMed]
Received: 22/05/2019
Accepted : 04/09/2019
In Press: 30/10/2019
Published: 28/07/2020
Abstract
OBJECTIVES:
Although articular cartilage contributes to smooth joint motion, once damaged this functionality cannot be recovered. Activation of the IL-6/STAT3 signalling pathway contributes to chondrogenic differentiation of mesenchymal stem cells (MSCs), indicating a role for soluble IL-6R (sIL-6R) during chondrogenesis in vitro. The aim of this study is to develop a novel therapeutic tool for regenerative medicine of articular cartilage.
METHODS:
Human bone marrow-derived MSCs were pre-treated with sIL-6R to direct their differentiation into chondrocytes, then seeded on a poly-lactic-co-glycolic acid (PLGA) sheet to enhance the localised residence of MSCs. The material was implanted into knee joint spaces of antigen-induced arthritis (AIA) rats, an animal model of rheumatoid arthritis (RA). After 8 weeks, the effects of the implantation on articular cartilage repair were assessed by x-ray image and staining with safranin O (S-O), aggrecan and human leukocyte antigen (HLA).
RESULTS:
Swelling of knees in AIA rats, but not sham-treated rats, was observed. AIA rats implanted with PLGA and sIL-6R-treated MSCs showed similar knee joint imaging to sham rats using x-ray; however, those with PLGA alone, or with PLGA with MSCs, did not. Rats implanted with PLGA and sIL-6R-treated MSCs, but not PLGA alone or PLGA with MSCs, showed positive imaging by S-O staining as well as human aggrecan. HLA was not detected in the knees of any of the rats.
CONCLUSIONS:
PLGA and sIL-6R-treated MSCs help to repair articular cartilage with high efficacy. Thus, the application of this promising strategy to regenerative medicine for articular cartilage in patients with RA is anticipated.
