Aguilera, YolandaMellado-Damas, NuriaOlmedo-Moreno, LauraLópez, VíctorPanadero-Morón, ConcepciónBenito, MarinaGuerrero-Cázares, HugoMárquez-Vega, CatalinaMartín-Montalvo, AlejandroCapilla-González, Vivian2022-10-192022-10-192021-03-09Aguilera 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.http://hdl.handle.net/10668/4260Mesenchymal 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.enAtribución 4.0 Internacionalhttp://creativecommons.org/licenses/by/4.0/Mesenchymal stem cellsCell therapyIntranasal deliveryBiosafetyNervous system disordersCélulas madre mesenquimatosasTratamiento basado en trasplante de células y tejidosContención de riesgos biológicosEnfermedades del sistema nerviosoMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::HumansMedical Subject Headings::Organisms::Eukaryota::AnimalsMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::MiceMedical Subject Headings::Phenomena and Processes::Metabolic Phenomena::Pharmacokinetics::Tissue DistributionMedical Subject Headings::Anatomy::Cells::Stem CellsMedical Subject Headings::Technology and Food and Beverages::Technology, Industry, and Agriculture::Technology::Quality ControlMedical Subject Headings::Diseases::Nervous System Diseases::Central Nervous System DiseasesMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Chemistry Techniques, Analytical::Spectrum Analysis::Magnetic Resonance SpectroscopyMedical Subject Headings::Anatomy::Fluids and Secretions::Body Fluids::Extracellular Fluid::PlasmaMedical Subject Headings::Diseases::Neoplasmsresearch article33803160open access10.3390/cancers130511692072-6694PMC7963187