RT Journal Article T1 Preclinical Safety Evaluation of Intranasally Delivered Human Mesenchymal Stem Cells in Juvenile Mice A1 Aguilera, Yolanda A1 Mellado-Damas, Nuria A1 Olmedo-Moreno, Laura A1 López, Víctor A1 Panadero-Morón, Concepción A1 Benito, Marina A1 Guerrero-Cázares, Hugo A1 Márquez-Vega, Catalina A1 Martín-Montalvo, Alejandro A1 Capilla-González, Vivian K1 Mesenchymal stem cells K1 Cell therapy K1 Intranasal delivery K1 Biosafety K1 Nervous system disorders K1 Células madre mesenquimatosas K1 Tratamiento basado en trasplante de células y tejidos K1 Contención de riesgos biológicos K1 Enfermedades del sistema nervioso AB Mesenchymal stem cell (MSC)-based therapy is a promising therapeutic approach in the management of several pathologies, including central nervous system diseases. Previously, we demonstrated the therapeutic potential of human adipose-derived MSCs for neurological sequelae of oncological radiotherapy using the intranasal route as a non-invasive delivery method. However, a comprehensive investigation of the safety of intranasal MSC treatment should be performed before clinical applications. Here, we cultured human MSCs in compliance with quality control standards and administrated repeated doses of cells into the nostrils of juvenile immunodeficient mice, mimicking the design of a subsequent clinical trial. Short- and long-term effects of cell administration were evaluated by in vivo and ex vivo studies. No serious adverse events were reported on mouse welfare, behavioral performances, and blood plasma analysis. Magnetic resonance study and histological analysis did not reveal tumor formation or other abnormalities in the examined organs of mice receiving MSCs. Biodistribution study reveals a progressive disappearance of transplanted cells that was further supported by an absent expression of human GAPDH gene in the major organs of transplanted mice. Our data indicate that the intranasal application of MSCs is a safe, simple and non-invasive strategy and encourage its use in future clinical trials. PB MDPI YR 2021 FD 2021-03-09 LK http://hdl.handle.net/10668/4260 UL http://hdl.handle.net/10668/4260 LA en NO Aguilera Y, Mellado-Damas N, Olmedo-Moreno L, López V, Panadero-Morón C, Benito M, et al. Preclinical Safety Evaluation of Intranasally Delivered Human Mesenchymal Stem Cells in Juvenile Mice. Cancers. 2021 Mar 9;13(5):1169. DS RISalud RD Apr 18, 2025