Autor: |
Tolomeo AM; Department of Cardiac, Thoracic and Vascular Science and Public Health, University of Padova, 35128 Padua, Italy.; L.i.f.e.L.a.b. Program, Consorzio per la Ricerca Sanitaria (CORIS), Veneto Region, 35128 Padua, Italy., Zuccolotto G; Istituto Oncologico Veneto IOV-Istituto di Ricovero e Cura a Carattere Scientifico IRCCS, 35128 Padua, Italy., Malvicini R; L.i.f.e.L.a.b. Program, Consorzio per la Ricerca Sanitaria (CORIS), Veneto Region, 35128 Padua, Italy.; Department of Women's and Children's Health, University of Padova, 35128 Padua, Italy.; Instituto de Medicina Traslacional, Trasplante y Bioingeniería, Universidad Favaloro-Consejo Nacional de Investigaciones Cientìficas y Técnicas, Buenos Aires 1078, Argentina., De Lazzari G; L.i.f.e.L.a.b. Program, Consorzio per la Ricerca Sanitaria (CORIS), Veneto Region, 35128 Padua, Italy.; Department of Women's and Children's Health, University of Padova, 35128 Padua, Italy., Penna A; Department of Surgery, Oncology and Gastroenterology, University of Padova, 35128 Padua, Italy., Franco C; Rheumatology Unit, Department of Medicine (DIMED), University of Padova, 35128 Padua, Italy., Caicci F; Department of Biology, University of Padova, 35131 Padua, Italy., Magarotto F; Department of Women's and Children's Health, University of Padova, 35128 Padua, Italy., Quarta S; Department of Medicine, University of Padova, 35128 Padua, Italy., Pozzobon M; Department of Women's and Children's Health, University of Padova, 35128 Padua, Italy.; Fondazione Istituto di Ricerca Pediatrica Città della Speranza, 35127 Padua, Italy., Rosato A; Istituto Oncologico Veneto IOV-Istituto di Ricovero e Cura a Carattere Scientifico IRCCS, 35128 Padua, Italy.; Department of Surgery, Oncology and Gastroenterology, University of Padova, 35128 Padua, Italy., Muraca M; L.i.f.e.L.a.b. Program, Consorzio per la Ricerca Sanitaria (CORIS), Veneto Region, 35128 Padua, Italy.; Department of Women's and Children's Health, University of Padova, 35128 Padua, Italy., Collino F; Laboratory of Translational Research in Paediatric Nephro-Urology, Department of Clinical Sciences and Community Health, University of Milano, 20122 Milan, Italy.; Fondazione Ca' Granda IRCCS Ospedale Maggiore Policlinico, 20122 Milan, Italy. |
Abstrakt: |
Mesenchymal stromal cell-derived extracellular vesicles (MSC-EVs) are extensively studied as therapeutic tools. Evaluation of their biodistribution is fundamental to understanding MSC-EVs' impact on target organs. In our work, MSC-EVs were initially labeled with DiR, a fluorescent lipophilic dye, and administered to BALB/c mice (2.00 × 10 10 EV/mice) through the following routes: intravenous (IV), intratracheal (IT) and intranasal (IN). DiR-labeled MSC-EVs were monitored immediately after injection, and after 3 and 24 hours (h). Whole-body analysis, 3 h after IV injection, showed an accumulation of MSC-EVs in the mice abdominal region, compared to IT and IN, where EVs mainly localized at the levels of the chest and brain region, respectively. After 24 h, EV-injected mice retained a stronger positivity in the same regions identified after 3 h from injection. The analyses of isolated organs confirmed the accumulation of EVs in the spleen and liver after IV administration. Twenty-four hours after the IT injection of MSC-EVs, a stronger positivity was detected selectively in the isolated lungs, while for IN, the signal was confined to the brain. In conclusion, these results show that local administration of EVs can increase their concentration in selective organs, limiting their systemic biodistribution and possibly the extra-organ effects. Biodistribution studies can help in the selection of the most appropriate way of administration of MSC-EVs for the treatment of different diseases. |