Abstract：
Current therapeutic approaches for chronic venous ulcers (CVUs) still require evidence of effectiveness. Diverse sources of extracellular vesicles (EVs) have been proposed for tissue regeneration, however the lack of potency tests, to predict in-vivo effectiveness, and a reliable scalability have delayed their clinical application. This study aimed to investigate whether autologous serum-derived EVs (s-EVs), recovered from patients with CVUs, may be a proper therapeutic approach to improve the healing process. A pilot case-control interventional study (CS2/1095/0090491) has been designed and s-EVs recovered from patients. Patient eligibility included two or more distinct chronic lesions in the same limb with 11 months as median persistence of active ulcer before enrollment. Patients were treated three times a week, for 2 weeks. Qualitative CVU analysis demonstrated that s-EVs-treated lesions displayed a higher percentage of granulation tissue compared to the control group (Sham) (s-EVs 3 out of 5: 75-100 % vs Sham: none), further confirmed at day 30. s-EVs-treated lesions also displayed higher sloughy tissue reduction at the end of treatment even increased at day 30. Additionally, s-EV treatment led to a median surface reduction of 151 mm2 compared to 84 mm2 in the Sham group, difference even more evident at day 30 (s-EVs 385 mm2vs Sham 106 mm2p = 0.004). Consistent with the enrichment of transforming growth factor-β1 in s-EVs, histological analyses showed a regenerative tissue with an increase in microvascular proliferation areas. This study first demonstrates the clinical effectiveness of autologous s-EVs in promoting the healing process of CVUs unresponsive to conventional treatments.
摘要：
目前慢性静脉性溃疡（CVU）的治疗方法仍然需要有效性的证据。细胞外囊泡（EV）的不同来源已被提出用于组织再生，然而缺乏效力测试，为了预测体内有效性，和可靠的可扩展性推迟了其临床应用。本研究旨在探讨自体血清来源的电动汽车(s-EV)从CVU患者中恢复，可能是改善愈合过程的适当治疗方法。已设计了一项试点病例对照介入研究（CS2/1095/0090491），并从患者中恢复了s-EV。患者的资格包括在同一肢体中的两个或更多个不同的慢性病变,其中11个月是在登记之前活动性溃疡的中位持续时间。患者每周接受三次治疗，2周。定性CVU分析表明，与对照组（Sham）相比，s-EV治疗的病变显示出较高的肉芽组织百分比（s-EV3/5：75-100％vsSham：无），在第30天进一步确认。s-EV治疗的病变在治疗结束时也显示出更高的疏松组织减少，甚至在第30天增加。此外,与Sham组的84mm2相比，s-EV处理导致中位表面减少151mm2，差异在第30天更加明显(s-EV385mm2vsSham106mm2p=0.004)。与转化生长因子β1在s-EV中的富集一致，组织学分析显示再生组织微血管增殖面积增加。这项研究首次证明了自体s-EV在促进对常规治疗无反应的CVU愈合过程中的临床有效性。
