In:
Frontiers in Pharmacology, Frontiers Media SA, Vol. 13 ( 2022-3-21)
Abstract:
Background: Osteoarthritis (OA) is the most common joint disorder, lacking disease-modifying treatments. Adipose-derived mesenchymal stem cells (ADSCs) are adult multipotent stromal cells obtained from fat tissue, which holds great potential in treating OA. This study aimed to evaluate the anti-OA efficacy of ADSCs from preclinical and clinical facets and explore the underlying mechanism of action. Methods: In vivo , a single dose of 5 × 10 5 ADSCs was injected into the knee joints of monoiodoacetate-induced OA rat model. The levels of metabolic and hypertrophic molecules (MMP13, Collagen II, Collagen X) of chondrocytes were measured by immunohistochemistry. In vitro , cell viability assay was conducted to detect the proliferation ability of chondrocytes treated with ADSCs conditioned medium (ADSCs-CM). Quantitative real-time polymerase chain reaction and Western blot assays were applied to explore the mechanism of action of ADSCs. Moreover, a retrospective analysis was conducted to determine the clinical efficacy and safety of ADSCs on OA patients. Results: The animal study showed that ADSCs significantly alleviated OA cartilage lesions in rats, as was confirmed by downregulation of the MMP13 and Collagen X and upregulation of the Collagen II. In vitro data showed that ADSCs-CM promoted the proliferation of chondrocytes, and significantly restored the IL-1β-induced abnormal expressions of molecular markers IL-6, Aggrecan, MMP3, MMP13, Collagen II, Collagen X, ADAMTS5, ADAMTS9, SOX6, and SOX9 in chondrocytes. Such regulatory effects of ADSCs-CM on the proliferation and these anabolic, catabolic, and hypertrophic markers of chondrocytes suggested a paracrine-based mode of action of ADSCs. Furthermore, the clinical data showed that ADSCs reduced pain and repaired cartilage damage in OA patients, with no adverse events. Conclusion: This study demonstrated the anti-OA efficacy, safety, and a paracrine-based mechanism of ADSCs, providing a promising cell-based therapeutic option for OA treatment.
Type of Medium:
Online Resource
ISSN:
1663-9812
DOI:
10.3389/fphar.2022.854025
DOI:
10.3389/fphar.2022.854025.s001
DOI:
10.3389/fphar.2022.854025.s002
DOI:
10.3389/fphar.2022.854025.s003
DOI:
10.3389/fphar.2022.854025.s004
DOI:
10.3389/fphar.2022.854025.s005
Language:
Unknown
Publisher:
Frontiers Media SA
Publication Date:
2022
detail.hit.zdb_id:
2587355-6
SSG:
15,3
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