Hydrogen generators-protected mesenchymal stem cells reverse articular redox imbalance-induced immune dysfunction for osteoarthritis treatment

IF 12.8 1区 医学 Q1 ENGINEERING, BIOMEDICAL
Zhou Xu , Ruilong Song , Zhiling Chen , Yu Sun , Yinhe Xia , Haixiang Miao , Weijie Wang , Yuankai Zhang , Xinyi Jiang , Gang Chen
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引用次数: 0

Abstract

Stem cell therapy has revolutionized the management of osteoarthritis (OA), but the articular dysregulated redox status diminishes cell engraftment efficiency and disrupts immune homeostasis, therefore compromising the overall therapeutic efficacy. Here, we present hydrogen (H2) generators-backpacked mesenchymal stem cells (MSCs) which preserve the biological functions and survival of transplanted cells and reverse articular immune dysfunction, mitigating OA. Specifically, post systemic transplantation, H2 generators-laden MSCs home to OA joints, and upon stimulation in acidic OA environment, H2 produced from the generators remodels articular redox balance, thereby relieving the loss of mitochondrial membrane potential, decreasing cell apoptosis rate, and maintaining pluripotent and paracrine functions of MSCs. Furthermore, the reactive oxygen species scavenging by H2 in combination with paracrine effects of the MSCs promote macrophage polarization towards the anti-inflammatory M2 phenotype, which contributes to reversing synovial immune disorder. In severe OA model, the backpacked MSCs reduce osteoarthritic degeneration, osteophyte formation and joint inflammation, and promote cartilage regeneration. In sum, our work demonstrates that arming with H2 generators effectively boosts the therapeutic efficacy of MSCs, which hold great potential for alleviating redox imbalance-related tissue lesions, including but not limited to OA.

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来源期刊
Biomaterials
Biomaterials 工程技术-材料科学:生物材料
CiteScore
26.00
自引率
2.90%
发文量
565
审稿时长
46 days
期刊介绍: Biomaterials is an international journal covering the science and clinical application of biomaterials. A biomaterial is now defined as a substance that has been engineered to take a form which, alone or as part of a complex system, is used to direct, by control of interactions with components of living systems, the course of any therapeutic or diagnostic procedure. It is the aim of the journal to provide a peer-reviewed forum for the publication of original papers and authoritative review and opinion papers dealing with the most important issues facing the use of biomaterials in clinical practice. The scope of the journal covers the wide range of physical, biological and chemical sciences that underpin the design of biomaterials and the clinical disciplines in which they are used. These sciences include polymer synthesis and characterization, drug and gene vector design, the biology of the host response, immunology and toxicology and self assembly at the nanoscale. Clinical applications include the therapies of medical technology and regenerative medicine in all clinical disciplines, and diagnostic systems that reply on innovative contrast and sensing agents. The journal is relevant to areas such as cancer diagnosis and therapy, implantable devices, drug delivery systems, gene vectors, bionanotechnology and tissue engineering.
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