Department of Experimental Biology, Wroclaw University of Environmental and Life Sciences, Norwida 27B street, A7 building, 50-375, Wroclaw, Poland.
International Institute of Translational Medicine, Malin, Jesionowa 11, 55-114, Wisznia Mała, Poland.
Stem Cell Res Ther. 2019 Dec 18;10(1):394. doi: 10.1186/s13287-019-1469-5.
In athlete horses, suspensory ligament (SL) injuries are the most common cause of lameness. Healing of SL injury is still problematic, and even proper rehabilitation and pharmacological therapy do not guarantee returning to the initial performance level. In our previous studies, we have shown that a combination of 5-azacytidine (AZA) and resveratrol (RES) exerts beneficial, rejuvenating effects on metabolic syndrome derived adipose-derived stem cells (ASCs). Thus, in the presented research, we investigate whether not only rejuvenated ASC but also microvesicles (MVs) secreted by them possess enhanced regenerative properties in SL injury.
In the presented study, a 6-year-old Dutch Warmblood gelding, working in jumping, was diagnosed with SL injury using ultrasonography, Doppler, real-time elastography and thermography. As a therapeutic strategy, the affected animal was treated with extracellular microvesicles derived from ASC treated with the combination of 5-azacytydine (AZA) and resveratrol (RES) (MVs) RESULTS: First, anti-apoptotic effects of MVs were tested in co-culture with metabolic syndrome derived ASC. The proliferation of cells and expression of pro-apoptotic genes were investigated. Then, MVs were injected directly into the injured SL of the Dutch Warmblood gelding. In vitro assays revealed that MVs enhance the proliferation of ASC and exert an anti-apoptotic effect. In the affected horse, the application of MVs resulted in increased lesion filling and improvement of angiogenesis and elasticity in injured tissue.
As MVs mimic several of the biological actions exerted by ASC, they have become an alternative for stem cell-based therapies and can be effectively applied for the treatment of SL injury in horses.
在运动员马匹中，悬韧带（SL）损伤是最常见的跛行原因。SL 损伤的愈合仍然存在问题，即使进行适当的康复和药物治疗也不能保证恢复到最初的运动水平。在我们之前的研究中，我们已经表明，5-氮杂胞苷（AZA）和白藜芦醇（RES）的组合对代谢综合征衍生的脂肪间充质干细胞（ASCs）具有有益的、恢复活力的作用。因此，在本研究中，我们研究了不仅是恢复活力的 ASC，而且它们分泌的微泡（MVs）是否在 SL 损伤中具有增强的再生特性。
在本研究中，一匹 6 岁的荷兰温血骟马，从事跳跃运动，通过超声、多普勒、实时弹性成像和热成像诊断出 SL 损伤。作为一种治疗策略，受影响的动物接受了用 5-氮杂胞苷（AZA）和白藜芦醇（RES）处理的 ASC 衍生的细胞外微泡（MVs）的治疗。
首先，在与代谢综合征衍生的 ASC 的共培养中测试了 MVs 的抗凋亡作用。研究了细胞的增殖和促凋亡基因的表达。然后，将 MVs 直接注射到荷兰温血骟马受伤的 SL 中。体外试验表明，MVs 可增强 ASC 的增殖，并发挥抗凋亡作用。在受影响的马中，MVs 的应用导致损伤部位的填充增加，并且受伤组织的血管生成和弹性得到改善。
由于 MVs 模拟了 ASC 发挥的几种生物学作用，因此它们已成为基于干细胞疗法的替代方法，并且可以有效地应用于马的 SL 损伤治疗。
