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Harnessing the ECM Microenvironment to Ameliorate Mesenchymal Stromal Cell-Based Therapy in Chronic Lung Diseases

Elowsson Rendin, Linda LU ; Löfdahl, Anna LU ; Kadefors, Måns LU ; Söderlund, Zackarias LU orcid ; Tykesson, Emil LU orcid ; Rolandsson Enes, Sara LU orcid ; Wigén, Jenny LU and Westergren-Thorsson, Gunilla LU orcid (2021) In Frontiers in Pharmacology 12.
Abstract

It is known that the cell environment such as biomechanical properties and extracellular matrix (ECM) composition dictate cell behaviour including migration, proliferation, and differentiation. Important constituents of the microenvironment, including ECM molecules such as proteoglycans and glycosaminoglycans (GAGs), determine events in both embryogenesis and repair of the adult lung. Mesenchymal stromal/stem cells (MSC) have been shown to have immunomodulatory properties and may be potent actors regulating tissue remodelling and regenerative cell responses upon lung injury. Using MSC in cell-based therapy holds promise for treatment of chronic lung diseases such as idiopathic pulmonary fibrosis (IPF) and chronic obstructive pulmonary... (More)

It is known that the cell environment such as biomechanical properties and extracellular matrix (ECM) composition dictate cell behaviour including migration, proliferation, and differentiation. Important constituents of the microenvironment, including ECM molecules such as proteoglycans and glycosaminoglycans (GAGs), determine events in both embryogenesis and repair of the adult lung. Mesenchymal stromal/stem cells (MSC) have been shown to have immunomodulatory properties and may be potent actors regulating tissue remodelling and regenerative cell responses upon lung injury. Using MSC in cell-based therapy holds promise for treatment of chronic lung diseases such as idiopathic pulmonary fibrosis (IPF) and chronic obstructive pulmonary disease (COPD). However, so far clinical trials with MSCs in COPD have not had a significant impact on disease amelioration nor on IPF, where low cell survival rate and pulmonary retention time are major hurdles to overcome. Research shows that the microenvironment has a profound impact on transplanted MSCs. In our studies on acellular lung tissue slices (lung scaffolds) from IPF patients versus healthy individuals, we see a profound effect on cellular activity, where healthy cells cultured in diseased lung scaffolds adapt and produce proteins further promoting a diseased environment, whereas cells on healthy scaffolds sustain a healthy proteomic profile. Therefore, modulating the environmental context for cell-based therapy may be a potent way to improve treatment using MSCs. In this review, we will describe the importance of the microenvironment for cell-based therapy in chronic lung diseases, how MSC-ECM interactions can affect therapeutic output and describe current progress in the field of cell-based therapy.

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author
; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
artificial lung scaffolds, chronic objective pulmonary disease, extracellular matrix, idiopathic pulmonary fibrosis, MSC
in
Frontiers in Pharmacology
volume
12
article number
645558
publisher
Frontiers Media S. A.
external identifiers
  • pmid:34040521
  • scopus:85104995818
ISSN
1663-9812
DOI
10.3389/fphar.2021.645558
language
English
LU publication?
yes
additional info
Publisher Copyright: © Copyright © 2021 Elowsson Rendin, Löfdahl, Kadefors, Söderlund, Tykesson, Rolandsson Enes, Wigén and Westergren-Thorsson. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.
id
a5f31ef0-cc20-4060-ba2d-c817121b8345
date added to LUP
2021-05-10 11:20:37
date last changed
2024-06-15 10:56:38
@article{a5f31ef0-cc20-4060-ba2d-c817121b8345,
  abstract     = {{<p>It is known that the cell environment such as biomechanical properties and extracellular matrix (ECM) composition dictate cell behaviour including migration, proliferation, and differentiation. Important constituents of the microenvironment, including ECM molecules such as proteoglycans and glycosaminoglycans (GAGs), determine events in both embryogenesis and repair of the adult lung. Mesenchymal stromal/stem cells (MSC) have been shown to have immunomodulatory properties and may be potent actors regulating tissue remodelling and regenerative cell responses upon lung injury. Using MSC in cell-based therapy holds promise for treatment of chronic lung diseases such as idiopathic pulmonary fibrosis (IPF) and chronic obstructive pulmonary disease (COPD). However, so far clinical trials with MSCs in COPD have not had a significant impact on disease amelioration nor on IPF, where low cell survival rate and pulmonary retention time are major hurdles to overcome. Research shows that the microenvironment has a profound impact on transplanted MSCs. In our studies on acellular lung tissue slices (lung scaffolds) from IPF patients versus healthy individuals, we see a profound effect on cellular activity, where healthy cells cultured in diseased lung scaffolds adapt and produce proteins further promoting a diseased environment, whereas cells on healthy scaffolds sustain a healthy proteomic profile. Therefore, modulating the environmental context for cell-based therapy may be a potent way to improve treatment using MSCs. In this review, we will describe the importance of the microenvironment for cell-based therapy in chronic lung diseases, how MSC-ECM interactions can affect therapeutic output and describe current progress in the field of cell-based therapy.</p>}},
  author       = {{Elowsson Rendin, Linda and Löfdahl, Anna and Kadefors, Måns and Söderlund, Zackarias and Tykesson, Emil and Rolandsson Enes, Sara and Wigén, Jenny and Westergren-Thorsson, Gunilla}},
  issn         = {{1663-9812}},
  keywords     = {{artificial lung scaffolds; chronic objective pulmonary disease; extracellular matrix; idiopathic pulmonary fibrosis; MSC}},
  language     = {{eng}},
  month        = {{04}},
  publisher    = {{Frontiers Media S. A.}},
  series       = {{Frontiers in Pharmacology}},
  title        = {{Harnessing the ECM Microenvironment to Ameliorate Mesenchymal Stromal Cell-Based Therapy in Chronic Lung Diseases}},
  url          = {{http://dx.doi.org/10.3389/fphar.2021.645558}},
  doi          = {{10.3389/fphar.2021.645558}},
  volume       = {{12}},
  year         = {{2021}},
}