4.6 Article

Preclinical Safety Evaluation of Intranasally Delivered Human Mesenchymal Stem Cells in Juvenile Mice

Journal

CANCERS
Volume 13, Issue 5, Pages -

Publisher

MDPI
DOI: 10.3390/cancers13051169

Keywords

mesenchymal stem cells; cell therapy; intranasal delivery; biosafety; nervous system disorders

Categories

Funding

  1. Andalusian Regional Ministry of Health [PI0272-2017]
  2. Institute of Health Carlos III - Fondos FEDER [PI20/00341, CP19/00046, PI18/01590, CPII19/00023]
  3. Fundacion Cientifica de la Asociacion Espanola Contra el Cancer [IDEAS20051CAPI]
  4. crowdfunding platform PRECIPITA of the Spanish Foundation for Science and Technology [2018-000237]
  5. Asociacion Pablo Ugarte (+ VIDA project)

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Utilizing mesenchymal stem cells through intranasal application is a safe and non-invasive strategy for treating neurological disorders, as evidenced by studies conducted on mice. The repeated doses of cells administered through the nostrils did not cause any serious adverse events or tumor formation, demonstrating the potential for future clinical trials. These findings support the use of intranasal MSC therapy for managing central nervous system diseases.
Simple Summary The concept of utilizing mesenchymal stem cells for the treatment of central nervous system disorders has progressed from preclinical studies to clinical trials. While promising, the effectiveness of cell therapy is hampered by the route used to deliver cells into the brain. In this context, intranasal cell administration has boomed over the past few years as an effective cell delivery method. However, comprehensive safety studies are required before translation to the clinic. Our study shed light on how intranasally administrated mesenchymal stem cells may be used to safely treat neurological disorders. 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.

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