First pilot case-control interventional study using autologous extracellular vesicles to treat chronic venous ulcers unresponsive to conventional treatments. (April 2023)

• Record Type: Journal Article
• Authors: Gibello, Lorenzo; D'Antico, Sergio; Salafia, Marika; Senetta, Rebecca; Pomatto, Margherita Alba Carlotta; Orlando, Giulia; Sarcinella, Alessandro; Lopatina, Tatiana; Quaglino, Pietro; Lorenzi, Marco; Verzini, Fabio; Camussi, Giovanni; Brizzi, Maria Felice
• Is Part Of: Pharmacological research. Volume 190(2023)
• Publication Date: 2023-04
• Subjects: AFOG acid fuchsine orange G -- CVU chronic venous ulcer -- BrdU bromodeoxyuridine -- EDQM European Directorate for the Quality of Medicines -- EVs extracellular vesicles -- FCS fetal calf serum -- GPGs good practice guidelines -- GMP good manufacturing practice -- H&E Hematoxylin and Eosin -- IQR interquartile range -- PAD peripheral artery disease -- PEG polyethylene glycol -- RPM revolution per minute -- s-EVs serum-derived extracellular vesicles -- TGFβ1 transforming growth factor-β -- VEGF vascular endothelial growth factor; Extracellular vesicles -- Venous ulcers -- Chronic wounds -- Tissue repair; Pharmacology -- Periodicals; Pharmacology -- Periodicals; Research -- Periodicals; Médicaments -- Recherche -- Périodiques; Pharmacologie -- Périodiques; 615.105
• DOI: 10.1016/j.phrs.2023.106718
• Languages: English
• ISSNs: 1043-6618

Abstract

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 mm 2 compared to 84 mm 2 in the Sham group, difference even more evident at day 30 (s-EVs 385 mm 2 vs Sham 106 mm 2 p = 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. Graphical Abstract: ga1