Biodistribution of Intratracheal, Intranasal, and Intravenous Injections of Human Mesenchymal Stromal Cell-Derived Extracellular Vesicles in a Mouse Model for Drug Delivery Studies
Anna Maria Tolomeo,
Gaia Zuccolotto,
Ricardo Malvicini,
Giada De Lazzari,
Alessandro Penna,
Chiara Franco,
Federico Caicci,
Fabio Magarotto,
Santina Quarta,
Michela Pozzobon,
Antonio Rosato,
Maurizio Muraca,
Federica Collino
Affiliations
Anna Maria Tolomeo
Department of Cardiac, Thoracic and Vascular Science and Public Health, University of Padova, 35128 Padua, Italy
Gaia Zuccolotto
Istituto Oncologico Veneto IOV-Istituto di Ricovero e Cura a Carattere Scientifico IRCCS, 35128 Padua, Italy
Ricardo Malvicini
L.i.f.e.L.a.b. Program, Consorzio per la Ricerca Sanitaria (CORIS), Veneto Region, 35128 Padua, Italy
Giada De Lazzari
L.i.f.e.L.a.b. Program, Consorzio per la Ricerca Sanitaria (CORIS), Veneto Region, 35128 Padua, Italy
Alessandro Penna
Department of Surgery, Oncology and Gastroenterology, University of Padova, 35128 Padua, Italy
Chiara Franco
Rheumatology Unit, Department of Medicine (DIMED), University of Padova, 35128 Padua, Italy
Federico Caicci
Department of Biology, University of Padova, 35131 Padua, Italy
Fabio Magarotto
Department of Women’s and Children’s Health, University of Padova, 35128 Padua, Italy
Santina Quarta
Department of Medicine, University of Padova, 35128 Padua, Italy
Michela Pozzobon
Department of Women’s and Children’s Health, University of Padova, 35128 Padua, Italy
Antonio Rosato
Istituto Oncologico Veneto IOV-Istituto di Ricovero e Cura a Carattere Scientifico IRCCS, 35128 Padua, Italy
Maurizio Muraca
L.i.f.e.L.a.b. Program, Consorzio per la Ricerca Sanitaria (CORIS), Veneto Region, 35128 Padua, Italy
Federica Collino
Laboratory of Translational Research in Paediatric Nephro-Urology, Department of Clinical Sciences and Community Health, University of Milano, 20122 Milan, Italy
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 × 1010 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.
