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The short-term and long-term effects of intranasal mesenchymal stem cell administration to noninflamed mice lung

Mesenchymal stem cells (mesenchymal stromal cells; MSC)-based therapies remain a promising approach to treat degenerative and inflammatory diseases. Their beneficial effects were confirmed in numerous experimental models and clinical trials. However, safety issues concerning MSCs’ stability and thei...

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Autores principales: Tynecka, Marlena, Janucik, Adrian, Niemira, Magdalena, Zbikowski, Arkadiusz, Stocker, Nino, Tarasik, Agnieszka, Starosz, Aleksandra, Grubczak, Kamil, Szalkowska, Anna, Korotko, Urszula, Reszec, Joanna, Kwasniewski, Miroslaw, Kretowski, Adam, Akdis, Cezmi, Sokolowska, Milena, Moniuszko, Marcin, Eljaszewicz, Andrzej
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9523259/
https://www.ncbi.nlm.nih.gov/pubmed/36189248
http://dx.doi.org/10.3389/fimmu.2022.967487
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author Tynecka, Marlena
Janucik, Adrian
Niemira, Magdalena
Zbikowski, Arkadiusz
Stocker, Nino
Tarasik, Agnieszka
Starosz, Aleksandra
Grubczak, Kamil
Szalkowska, Anna
Korotko, Urszula
Reszec, Joanna
Kwasniewski, Miroslaw
Kretowski, Adam
Akdis, Cezmi
Sokolowska, Milena
Moniuszko, Marcin
Eljaszewicz, Andrzej
author_facet Tynecka, Marlena
Janucik, Adrian
Niemira, Magdalena
Zbikowski, Arkadiusz
Stocker, Nino
Tarasik, Agnieszka
Starosz, Aleksandra
Grubczak, Kamil
Szalkowska, Anna
Korotko, Urszula
Reszec, Joanna
Kwasniewski, Miroslaw
Kretowski, Adam
Akdis, Cezmi
Sokolowska, Milena
Moniuszko, Marcin
Eljaszewicz, Andrzej
author_sort Tynecka, Marlena
collection PubMed
description Mesenchymal stem cells (mesenchymal stromal cells; MSC)-based therapies remain a promising approach to treat degenerative and inflammatory diseases. Their beneficial effects were confirmed in numerous experimental models and clinical trials. However, safety issues concerning MSCs’ stability and their long-term effects limit their implementation in clinical practice, including treatment of respiratory diseases such as asthma, chronic obstructive pulmonary disease, and COVID-19. Here, we aimed to investigate the safety of intranasal application of human adipose tissue-derived MSCs in a preclinical experimental mice model and elucidate their effects on the lungs. We assessed short-term (two days) and long-term (nine days) effects of MSCs administration on lung morphology, immune responses, epithelial barrier function, and transcriptomic profiles. We observed an increased frequency of IFNγ- producing T cells and a decrease in occludin and claudin 3 as a long-term effect of MSCs administration. We also found changes in the lung transcriptomic profiles, reflecting redox imbalance and hypoxia signaling pathway. Additionally, we found dysregulation in genes clustered in pattern recognition receptors, macrophage activation, oxidative stress, and phagocytosis. Our results suggest that i.n. MSCs administration to noninflamed healthy lungs induces, in the late stages, low-grade inflammatory responses aiming at the clearance of MSCs graft.
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spelling pubmed-95232592022-10-01 The short-term and long-term effects of intranasal mesenchymal stem cell administration to noninflamed mice lung Tynecka, Marlena Janucik, Adrian Niemira, Magdalena Zbikowski, Arkadiusz Stocker, Nino Tarasik, Agnieszka Starosz, Aleksandra Grubczak, Kamil Szalkowska, Anna Korotko, Urszula Reszec, Joanna Kwasniewski, Miroslaw Kretowski, Adam Akdis, Cezmi Sokolowska, Milena Moniuszko, Marcin Eljaszewicz, Andrzej Front Immunol Immunology Mesenchymal stem cells (mesenchymal stromal cells; MSC)-based therapies remain a promising approach to treat degenerative and inflammatory diseases. Their beneficial effects were confirmed in numerous experimental models and clinical trials. However, safety issues concerning MSCs’ stability and their long-term effects limit their implementation in clinical practice, including treatment of respiratory diseases such as asthma, chronic obstructive pulmonary disease, and COVID-19. Here, we aimed to investigate the safety of intranasal application of human adipose tissue-derived MSCs in a preclinical experimental mice model and elucidate their effects on the lungs. We assessed short-term (two days) and long-term (nine days) effects of MSCs administration on lung morphology, immune responses, epithelial barrier function, and transcriptomic profiles. We observed an increased frequency of IFNγ- producing T cells and a decrease in occludin and claudin 3 as a long-term effect of MSCs administration. We also found changes in the lung transcriptomic profiles, reflecting redox imbalance and hypoxia signaling pathway. Additionally, we found dysregulation in genes clustered in pattern recognition receptors, macrophage activation, oxidative stress, and phagocytosis. Our results suggest that i.n. MSCs administration to noninflamed healthy lungs induces, in the late stages, low-grade inflammatory responses aiming at the clearance of MSCs graft. Frontiers Media S.A. 2022-09-16 /pmc/articles/PMC9523259/ /pubmed/36189248 http://dx.doi.org/10.3389/fimmu.2022.967487 Text en Copyright © 2022 Tynecka, Janucik, Niemira, Zbikowski, Stocker, Tarasik, Starosz, Grubczak, Szalkowska, Korotko, Reszec, Kwasniewski, Kretowski, Akdis, Sokolowska, Moniuszko and Eljaszewicz https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Tynecka, Marlena
Janucik, Adrian
Niemira, Magdalena
Zbikowski, Arkadiusz
Stocker, Nino
Tarasik, Agnieszka
Starosz, Aleksandra
Grubczak, Kamil
Szalkowska, Anna
Korotko, Urszula
Reszec, Joanna
Kwasniewski, Miroslaw
Kretowski, Adam
Akdis, Cezmi
Sokolowska, Milena
Moniuszko, Marcin
Eljaszewicz, Andrzej
The short-term and long-term effects of intranasal mesenchymal stem cell administration to noninflamed mice lung
title The short-term and long-term effects of intranasal mesenchymal stem cell administration to noninflamed mice lung
title_full The short-term and long-term effects of intranasal mesenchymal stem cell administration to noninflamed mice lung
title_fullStr The short-term and long-term effects of intranasal mesenchymal stem cell administration to noninflamed mice lung
title_full_unstemmed The short-term and long-term effects of intranasal mesenchymal stem cell administration to noninflamed mice lung
title_short The short-term and long-term effects of intranasal mesenchymal stem cell administration to noninflamed mice lung
title_sort short-term and long-term effects of intranasal mesenchymal stem cell administration to noninflamed mice lung
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9523259/
https://www.ncbi.nlm.nih.gov/pubmed/36189248
http://dx.doi.org/10.3389/fimmu.2022.967487
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