Human umbilical-cord-derived mesenchymal stem cells in combination with rapamycin reduce cartilage degradation via inhibition of the AKT/mTOR signaling pathway.
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引用次数: 0
Abstract
Background and aims: Mesenchymal stem cell (MSC) therapy is a promising strategy for treating osteoarthritis (OA). However, the inflammatory microenvironment, apoptosis of transplanted cells, and shear forces during direct injection limit the therapeutic efficacy. This study aimed to explore the role of rapamycin combined with human umbilical-cord-derived mesenchymal stem cells (hUMSCs) in OA rabbits in vivo.
Methods: OA rabbits received an intra-articular injection of a collagenase solution. Gross observations, X-ray examinations, and histological examinations were performed to detect cartilage degradation levels. The fluorescent membrane dye DiR was used to label hUMSCs. In the combination therapy group, rapamycin was injected into the rabbit knee joint one day post the intra-articular injection of hUMSCs. Bioinformatics and transcriptome profiling of the knee meniscus were used to evaluate the potential molecular mechanisms of the combination therapy.
Results: Our study shows that rapamycin combined with hUMSCs significantly ameliorated OA severity in vivo, enhancing matrix synthesis and promoting cartilage repair. The combination therapy was more efficient than rapamycin or hUMSC treatment alone. Moreover, bioinformatics and transcriptomic analyses revealed that combination therapy might enhance autophagy in chondrocytes, partially by inhibiting the mTOR pathway.
Conclusions: Our study indicates that the combination therapy of rapamycin and hUMSCs may promote cartilage repair in OA rabbits through the mTOR pathway and offers a novel approach for OA therapy.
The translational potential of this article: Our study provides new evidence to support the use of hUMSCs in combination with rapamycin as a potential candidate for OA treatment.
期刊介绍:
The journal Immunopharmacology and Immunotoxicology is devoted to pre-clinical and clinical drug discovery and development targeting the immune system. Research related to the immunoregulatory effects of various compounds, including small-molecule drugs and biologics, on immunocompetent cells and immune responses, as well as the immunotoxicity exerted by xenobiotics and drugs. Only research that describe the mechanisms of specific compounds (not extracts) is of interest to the journal.
The journal will prioritise preclinical and clinical studies on immunotherapy of disorders such as chronic inflammation, allergy, autoimmunity, cancer etc. The effects of small-drugs, vaccines and biologics against central immunological targets as well as cell-based therapy, including dendritic cell therapy, T cell adoptive transfer and stem cell therapy, are topics of particular interest. Publications pointing towards potential new drug targets within the immune system or novel technology for immunopharmacological drug development are also welcome.
With an immunoscience focus on drug development, immunotherapy and toxicology, the journal will cover areas such as infection, allergy, inflammation, tumor immunology, degenerative disorders, immunodeficiencies, neurology, atherosclerosis and more.
Immunopharmacology and Immunotoxicology will accept original manuscripts, brief communications, commentaries, mini-reviews, reviews, clinical trials and clinical cases, on the condition that the results reported are based on original, clinical, or basic research that has not been published elsewhere in any journal in any language (except in abstract form relating to paper communicated to scientific meetings and symposiums).