Preclinical Safety Evaluation of Intranasally Delivered Human Mesenchymal Stem Cells in Juvenile Mice
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...
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doaj-e5145f4b7c8c4d94ad87f270ff2c90f82021-03-10T00:01:30ZengMDPI AGCancers2072-66942021-03-01131169116910.3390/cancers13051169Preclinical Safety Evaluation of Intranasally Delivered Human Mesenchymal Stem Cells in Juvenile MiceYolanda Aguilera0Nuria Mellado-Damas1Laura Olmedo-Moreno2Víctor López3Concepción Panadero-Morón4Marina Benito5Hugo Guerrero-Cázares6Catalina Márquez-Vega7Alejandro Martín-Montalvo8Vivian Capilla-González9Andalusian Molecular Biology and Regenerative Medicine Centre (CABIMER)-CSIC-US-UPO, Department of Regeneration and Cell Therapy, 41092 Seville, SpainAndalusian Molecular Biology and Regenerative Medicine Centre (CABIMER)-CSIC-US-UPO, Department of Regeneration and Cell Therapy, 41092 Seville, SpainAndalusian Molecular Biology and Regenerative Medicine Centre (CABIMER)-CSIC-US-UPO, Department of Regeneration and Cell Therapy, 41092 Seville, SpainAndalusian Molecular Biology and Regenerative Medicine Centre (CABIMER)-CSIC-US-UPO, Department of Regeneration and Cell Therapy, 41092 Seville, SpainAndalusian Molecular Biology and Regenerative Medicine Centre (CABIMER)-CSIC-US-UPO, Department of Regeneration and Cell Therapy, 41092 Seville, SpainResearch Magnetic Resonance Unit, Hospital Nacional de Parapléjicos, 45004 Toledo, SpainDepartment of Neurosurgery, Mayo Clinic, Jacksonville, 32224 FL, USAPediatric Oncology Unit, Hospital Virgen del Rocio, 41013 Seville, SpainAndalusian Molecular Biology and Regenerative Medicine Centre (CABIMER)-CSIC-US-UPO, Department of Regeneration and Cell Therapy, 41092 Seville, SpainAndalusian Molecular Biology and Regenerative Medicine Centre (CABIMER)-CSIC-US-UPO, Department of Regeneration and Cell Therapy, 41092 Seville, SpainMesenchymal 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.https://www.mdpi.com/2072-6694/13/5/1169mesenchymal stem cellscell therapyintranasal deliverybiosafetynervous system disorders |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
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 |
spellingShingle |
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 Preclinical Safety Evaluation of Intranasally Delivered Human Mesenchymal Stem Cells in Juvenile Mice Cancers mesenchymal stem cells cell therapy intranasal delivery biosafety nervous system disorders |
author_facet |
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 |
author_sort |
Yolanda Aguilera |
title |
Preclinical Safety Evaluation of Intranasally Delivered Human Mesenchymal Stem Cells in Juvenile Mice |
title_short |
Preclinical Safety Evaluation of Intranasally Delivered Human Mesenchymal Stem Cells in Juvenile Mice |
title_full |
Preclinical Safety Evaluation of Intranasally Delivered Human Mesenchymal Stem Cells in Juvenile Mice |
title_fullStr |
Preclinical Safety Evaluation of Intranasally Delivered Human Mesenchymal Stem Cells in Juvenile Mice |
title_full_unstemmed |
Preclinical Safety Evaluation of Intranasally Delivered Human Mesenchymal Stem Cells in Juvenile Mice |
title_sort |
preclinical safety evaluation of intranasally delivered human mesenchymal stem cells in juvenile mice |
publisher |
MDPI AG |
series |
Cancers |
issn |
2072-6694 |
publishDate |
2021-03-01 |
description |
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. |
topic |
mesenchymal stem cells cell therapy intranasal delivery biosafety nervous system disorders |
url |
https://www.mdpi.com/2072-6694/13/5/1169 |
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