Extracellular vesicles in the treatment and prevention of osteoarthritis: can horses help us translate this therapy to humans?

Thomas J O'Brien, Fiona Hollinshead, Laurie R Goodrich
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Abstract

Osteoarthritis (OA) is a common joint disease affecting humans and horses, resulting in significant morbidity, financial expense, and loss of athletic use. While the pathogenesis is incompletely understood, inflammation is considered crucial in the development and progression of the disease. Mesenchymal stromal cells (MSCs) have received increasing scientific attention for their anti-inflammatory, immunomodulatory, and pro-regenerative effects. However, there are concerns about their ability to become a commercially available therapeutic. Extracellular vesicles (EVs) are now recognized to play a crucial role in the therapeutic efficacy observed with MSCs and offer a potentially novel cell-free therapeutic that may negate many of the concerns with MSCs. There is evidence that EVs have profound anti-inflammatory, immunomodulatory, and pro-regenerative effects equal to or greater than the MSCs they are derived from in the treatment of OA. Most of these studies are in small animal models, limiting the translation of these results to humans. However, highly translational animal models are crucial for further understanding the efficacy of potential therapeutics and for close comparisons with humans. For this reason, the horse, which experiences the same gravitational impacts on joints similar to people, is a highly relevant large animal species for testing. The equine species has well-designed and validated OA models, and additionally, therapies can be further tested in naturally occurring OA to validate preclinical model testing. Therefore, the horse is a highly suitable model to increase our knowledge of the therapeutic potential of EVs.

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治疗和预防骨关节炎的细胞外小泡:马能帮助我们将这种疗法应用于人类吗?
骨关节炎(OA)是一种影响人类和马匹的常见关节疾病,导致严重的发病率、经济支出和运动功能丧失。虽然发病机制尚不完全清楚,但炎症被认为在疾病的发展和进展中至关重要。间充质基质细胞(MSCs)因其抗炎、免疫调节和促再生作用而受到越来越多的科学关注。然而,人们对它们成为商业上可用的治疗药物的能力表示担忧。细胞外囊泡(EVs)现在被认为在MSCs的治疗效果中发挥着至关重要的作用,并提供了一种潜在的新的无细胞治疗方法,可以消除MSCs的许多担忧。有证据表明,EVs在OA治疗中具有与MSCs相同或更大的抗炎、免疫调节和促再生作用。这些研究大多是在小动物模型中进行的,这限制了这些结果对人类的转化。然而,高度转化的动物模型对于进一步了解潜在疗法的疗效以及与人类进行密切比较至关重要。因此,马对与人相似的关节产生了同样的重力影响,是一种非常适合测试的大型动物物种。马有精心设计和验证的OA模型,此外,可以在自然发生的OA中进一步测试疗法,以验证临床前模型测试。因此,马是一种非常适合增加我们对EVs治疗潜力的了解的模型。
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