Functional enhancement strategies to potentiate the therapeutic properties of mesenchymal stromal cells for respiratory diseases

Respiratory diseases remain a major health concern worldwide because they subject patients to considerable financial and psychosocial burdens and result in a high rate of morbidity and mortality. Although significant progress has been made in understanding the underlying pathologic mechanisms of sev...

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Main Authors: Miquéias Lopes-Pacheco, Patricia R. M. Rocco
Format: Article
Language:English
Published: Frontiers Media S.A. 2023-03-01
Series:Frontiers in Pharmacology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fphar.2023.1067422/full
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author Miquéias Lopes-Pacheco
Patricia R. M. Rocco
author_facet Miquéias Lopes-Pacheco
Patricia R. M. Rocco
author_sort Miquéias Lopes-Pacheco
collection DOAJ
description Respiratory diseases remain a major health concern worldwide because they subject patients to considerable financial and psychosocial burdens and result in a high rate of morbidity and mortality. Although significant progress has been made in understanding the underlying pathologic mechanisms of severe respiratory diseases, most therapies are supportive, aiming to mitigate symptoms and slow down their progressive course but cannot improve lung function or reverse tissue remodeling. Mesenchymal stromal cells (MSCs) are at the forefront of the regenerative medicine field due to their unique biomedical potential in promoting immunomodulation, anti-inflammatory, anti-apoptotic and antimicrobial activities, and tissue repair in various experimental models. However, despite several years of preclinical research on MSCs, therapeutic outcomes have fallen far short in early-stage clinical trials for respiratory diseases. This limited efficacy has been associated with several factors, such as reduced MSC homing, survival, and infusion in the late course of lung disease. Accordingly, genetic engineering and preconditioning methods have emerged as functional enhancement strategies to potentiate the therapeutic actions of MSCs and thus achieve better clinical outcomes. This narrative review describes various strategies that have been investigated in the experimental setting to functionally potentiate the therapeutic properties of MSCs for respiratory diseases. These include changes in culture conditions, exposure of MSCs to inflammatory environments, pharmacological agents or other substances, and genetic manipulation for enhanced and sustained expression of genes of interest. Future directions and challenges in efficiently translating MSC research into clinical practice are discussed.
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spelling doaj.art-74b3b73afd7c4b349299b3c62d3e77982023-03-16T04:25:25ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122023-03-011410.3389/fphar.2023.10674221067422Functional enhancement strategies to potentiate the therapeutic properties of mesenchymal stromal cells for respiratory diseasesMiquéias Lopes-Pacheco0Patricia R. M. Rocco1Biosystems & Integrative Sciences Institute, Faculty of Sciences, University of Lisbon, Lisbon, PortugalLaboratory of Pulmonary Investigation, Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro, BrazilRespiratory diseases remain a major health concern worldwide because they subject patients to considerable financial and psychosocial burdens and result in a high rate of morbidity and mortality. Although significant progress has been made in understanding the underlying pathologic mechanisms of severe respiratory diseases, most therapies are supportive, aiming to mitigate symptoms and slow down their progressive course but cannot improve lung function or reverse tissue remodeling. Mesenchymal stromal cells (MSCs) are at the forefront of the regenerative medicine field due to their unique biomedical potential in promoting immunomodulation, anti-inflammatory, anti-apoptotic and antimicrobial activities, and tissue repair in various experimental models. However, despite several years of preclinical research on MSCs, therapeutic outcomes have fallen far short in early-stage clinical trials for respiratory diseases. This limited efficacy has been associated with several factors, such as reduced MSC homing, survival, and infusion in the late course of lung disease. Accordingly, genetic engineering and preconditioning methods have emerged as functional enhancement strategies to potentiate the therapeutic actions of MSCs and thus achieve better clinical outcomes. This narrative review describes various strategies that have been investigated in the experimental setting to functionally potentiate the therapeutic properties of MSCs for respiratory diseases. These include changes in culture conditions, exposure of MSCs to inflammatory environments, pharmacological agents or other substances, and genetic manipulation for enhanced and sustained expression of genes of interest. Future directions and challenges in efficiently translating MSC research into clinical practice are discussed.https://www.frontiersin.org/articles/10.3389/fphar.2023.1067422/fullcell therapygenetic engineeringimmunomodulationinflammationlungpreconditioning
spellingShingle Miquéias Lopes-Pacheco
Patricia R. M. Rocco
Functional enhancement strategies to potentiate the therapeutic properties of mesenchymal stromal cells for respiratory diseases
Frontiers in Pharmacology
cell therapy
genetic engineering
immunomodulation
inflammation
lung
preconditioning
title Functional enhancement strategies to potentiate the therapeutic properties of mesenchymal stromal cells for respiratory diseases
title_full Functional enhancement strategies to potentiate the therapeutic properties of mesenchymal stromal cells for respiratory diseases
title_fullStr Functional enhancement strategies to potentiate the therapeutic properties of mesenchymal stromal cells for respiratory diseases
title_full_unstemmed Functional enhancement strategies to potentiate the therapeutic properties of mesenchymal stromal cells for respiratory diseases
title_short Functional enhancement strategies to potentiate the therapeutic properties of mesenchymal stromal cells for respiratory diseases
title_sort functional enhancement strategies to potentiate the therapeutic properties of mesenchymal stromal cells for respiratory diseases
topic cell therapy
genetic engineering
immunomodulation
inflammation
lung
preconditioning
url https://www.frontiersin.org/articles/10.3389/fphar.2023.1067422/full
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