TY - JOUR
T1 - Preclinical safety evaluation of intranasally delivered human mesenchymal stem cells in juvenile mice
AU - Aguilera, Yolanda
AU - Mellado-Damas, Nuria
AU - Olmedo-Moreno, Laura
AU - López, Víctor
AU - Panadero-Morón, Concepción
AU - Benito, Marina
AU - Guerrero-Cázares, Hugo
AU - Márquez-Vega, Catalina
AU - Martín-Montalvo, Alejandro
AU - Capilla-González, Vivian
N1 - Publisher Copyright:
© 2021 by the author. Licensee MDPI, Basel, Switzerland.
PY - 2021/3/1
Y1 - 2021/3/1
N2 - 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.
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 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.
KW - Biosafety
KW - Cell therapy
KW - Intranasal delivery
KW - Mesenchymal stem cells
KW - Nervous system dis-orders
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U2 - 10.3390/cancers13051169
DO - 10.3390/cancers13051169
M3 - Article
AN - SCOPUS:85102101881
SN - 2072-6694
VL - 13
SP - 1
EP - 18
JO - Cancers
JF - Cancers
IS - 5
M1 - 1169
ER -