Preclinical safety evaluation of intranasally delivered human mesenchymal stem cells in juvenile mice

Yolanda Aguilera, Nuria Mellado-Damas, Laura Olmedo-Moreno, Víctor López, Concepción Panadero-Morón, Marina Benito, Hugo Guerrero-Cázares, Catalina Márquez-Vega, Alejandro Martín-Montalvo, Vivian Capilla-González

Research output: Contribution to journalArticlepeer-review

Abstract

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 be-fore clinical applications. Here, we cultured human MSCs in compliance with quality control stand-ards 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.

Original languageEnglish (US)
Article number1169
Pages (from-to)1-18
Number of pages18
JournalCancers
Volume13
Issue number5
DOIs
StatePublished - Mar 1 2021

Keywords

  • Biosafety
  • Cell therapy
  • Intranasal delivery
  • Mesenchymal stem cells
  • Nervous system dis-orders

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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