Therapeutic Perspectives for Inflammation and Senescence in Osteoarthritis Using Mesenchymal Stem Cells, Mesenchymal Stem Cell-Derived Extracellular Vesicles and Senolytic Agents.
Therapeutic Perspectives for Inflammation and Senescence in Osteoarthritis Using Mesenchymal Stem Cells, Mesenchymal Stem Cell-Derived Extracellular Vesicles and Senolytic Agents.
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使用间充质干细胞，间充质干细胞衍生的细胞外囊泡和鼻溶性剂的骨关节炎炎症和衰老的治疗视角。
DOI：
10.3390/cells12101421
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发表时间：
2023-05-18
期刊：
影响因子：
6
通讯作者：
Kouroupis, Dimitrios
中科院分区：
文献类型：
--
作者：
Rizzo, Michael G. G.;Best, Thomas M. M.;Huard, Johnny;Philippon, Marc;Hornicek, Francis;Duan, Zhenfeng;Griswold, Anthony J. J.;Kaplan, Lee D. D.;Hare, Joshua M. M.;Kouroupis, Dimitrios
关键词：
骨关节炎（OA）是全世界老年人残疾的最常见原因。令人担忧的是，40岁以下人群中OA的发病率正在上升，这可能是由于肥胖和创伤后骨关节炎（PTOA）的增加。近年来，由于更好地了解OA的基础病理生理学，已经确定了几种针对特定分子通路的潜在治疗方法。特别是，炎症和免疫系统的作用已越来越多地被认为是在各种肌肉骨骼疾病，包括骨关节炎的重要。类似地，较高水平的宿主细胞衰老，其特征在于细胞分裂的停止和局部组织微环境内衰老相关分泌表型（SASP）的分泌，也与OA及其进展有关。该领域的新进展，包括干细胞疗法和衰老清除剂，正在出现，目标是减缓疾病进展。间充质干细胞/基质细胞（MSC）是多能成体干细胞的一个子集，已证明其具有调节未检查的炎症、逆转纤维化、减轻疼痛和潜在治疗OA患者的潜力。许多研究已经证明了MSC细胞外囊泡（EV）作为符合FDA规定的无细胞治疗的潜力。EV，包括外泌体和微泡，由许多细胞类型释放，并且越来越多地被认为在包括OA在内的年龄相关疾病的细胞间通讯中发挥关键作用。正在开发针对衰老细胞和SASP的旁分泌和自分泌分泌的OA治疗策略。这篇文章强调了MSC或MSC衍生产品单独或与senolytics组合控制患者症状并可能缓解OA进展的令人鼓舞的潜力。我们还将探索基因组学原理在OA研究中的应用，以及发现OA表型的潜力，这些表型可以激发更精确的患者驱动治疗。
Osteoarthritis (OA) is the most common cause of disability worldwide among the elderly. Alarmingly, the incidence of OA in individuals less than 40 years of age is rising, likely due to the increase in obesity and post-traumatic osteoarthritis (PTOA). In recent years, due to a better understanding of the underlying pathophysiology of OA, several potential therapeutic approaches targeting specific molecular pathways have been identified. In particular, the role of inflammation and the immune system has been increasingly recognized as important in a variety of musculoskeletal diseases, including OA. Similarly, higher levels of host cellular senescence, characterized by cessation of cell division and the secretion of a senescence-associated secretory phenotype (SASP) within the local tissue microenvironments, have also been linked to OA and its progression. New advances in the field, including stem cell therapies and senolytics, are emerging with the goal of slowing disease progression. Mesenchymal stem/stromal cells (MSCs) are a subset of multipotent adult stem cells that have demonstrated the potential to modulate unchecked inflammation, reverse fibrosis, attenuate pain, and potentially treat patients with OA. Numerous studies have demonstrated the potential of MSC extracellular vesicles (EVs) as cell-free treatments that comply with FDA regulations. EVs, including exosomes and microvesicles, are released by numerous cell types and are increasingly recognized as playing a critical role in cell–cell communication in age-related diseases, including OA. Treatment strategies for OA are being developed that target senescent cells and the paracrine and autocrine secretions of SASP. This article highlights the encouraging potential for MSC or MSC-derived products alone or in combination with senolytics to control patient symptoms and potentially mitigate the progression of OA. We will also explore the application of genomic principles to the study of OA and the potential for the discovery of OA phenotypes that can motivate more precise patient-driven treatments.
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影响因子：
23.9
作者：
Caplan AI;Correa D
通讯作者：
Correa D
影响因子：
64.8
作者：
Baker DJ;Childs BG;Durik M;Wijers ME;Sieben CJ;Zhong J;Saltness RA;Jeganathan KB;Verzosa GC;Pezeshki A;Khazaie K;Miller JD;van Deursen JM
通讯作者：
van Deursen JM
DOI：
10.1111/j.1365-2222.2010.03685.x
发表时间：
2011-04
期刊：
Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology
影响因子：
--
作者：
Brown JM;Nemeth K;Kushnir-Sukhov NM;Metcalfe DD;Mezey E
通讯作者：
Mezey E
影响因子：
2.4
作者：
Bongiovanni L;Andriessen A;Wauben MHM;Nolte-'t Hoen ENM;de Bruin A
通讯作者：
de Bruin A
影响因子：
82.9
作者：
Chaib, Selim;Tchkonia, Tamar;Kirkland, James L.
通讯作者：
Kirkland, James L.