Understanding the effects of mesenchymal stromal cell therapy for treating osteoarthritis using an in vitro co-culture model.

Shang, V; Li, J; Little, CB; Li, JJ

Understanding the effects of mesenchymal stromal cell therapy for treating osteoarthritis using an in vitro co-culture model.

Shang, V Li, J

Little, CB Li, JJ

Permalink

Publisher:: AO RESEARCH INSTITUTE DAVOS-ARI
Publication Type:: Journal Article
Citation:: Eur Cell Mater, 2023, 45, pp. 143-157
Issue Date:: 2023-06-19

Open Access

Copyright Clearance Process

Recently Added
In Progress
Open Access

This item is open access.

Adobe PDF

Download Published versionAdobe PDF (5 MB)

View on publisher's site

View statistics

Full metadata record

Field	Value	Language
dc.contributor.author	Shang, V
dc.contributor.author	Li, J https://orcid.org/0000-0002-3584-6765
dc.contributor.author	Little, CB
dc.contributor.author	Li, JJ
dc.date.accessioned	2024-04-29T08:09:47Z
dc.date.available	2024-04-29T08:09:47Z
dc.date.issued	2023-06-19
dc.identifier.citation	Eur Cell Mater, 2023, 45, pp. 143-157
dc.identifier.issn	1473-2262
dc.identifier.issn	1473-2262
dc.identifier.uri	http://hdl.handle.net/10453/178466
dc.description.abstract	Osteoarthritis (OA) is a leading cause of chronic pain and disability, for which there is no cure. Mesenchymal stromal cells (MSCs) have been used in clinical trials for treating OA due to their unique ability to generate paracrine anti-inflammatory and trophic signals. Interestingly, these studies have shown mainly short-term effects of MSCs in improving pain and joint function, rather than sustained and consistent benefits. This may reflect a change or loss in the therapeutic effects of MSCs after intra-articular injection. The present study aimed to unravel the reasons behind the variable efficacy of MSC injections for OA using an in vitro co-culture model. Osteoarthritic human synovial fibroblasts (OA-HSFs) were co-cultured with MSCs to investigate their reciprocal effects on cell responses and whether a short-term exposure of OA cells to MSCs was sufficient for reducing their diseased characteristics in a sustained manner. Gene expression and histological analyses were performed. OA-HSFs exposed to MSCs showed short-term downregulation of inflammatory markers. However, the MSCs showed upregulation of inflammatory markers and impaired ability to undergo osteogenesis and chondrogenesis in the presence of OA-HSFs. Moreover, short-term exposure of OA-HSFs to MSCs was found to be insufficient for inducing sustained changes to their diseased behaviour. These findings suggested that MSCs may not provide long-term effects in correcting the OA joint environment due to them adopting the diseased phenotype of the surrounding tissues, which has important implications for the future development of effective stem-cell-based OA treatments with long-term therapeutic efficacy.
dc.format	Electronic
dc.language	eng
dc.publisher	AO RESEARCH INSTITUTE DAVOS-ARI
dc.relation.ispartof	Eur Cell Mater
dc.relation.isbasedon	10.22203/eCM.v045a10
dc.rights	info:eu-repo/semantics/openAccess
dc.subject	0601 Biochemistry and Cell Biology, 0903 Biomedical Engineering
dc.subject.classification	Biomedical Engineering
dc.subject.classification	4003 Biomedical engineering
dc.subject.mesh	Humans
dc.subject.mesh	Coculture Techniques
dc.subject.mesh	Osteoarthritis
dc.subject.mesh	Interleukin-6
dc.subject.mesh	Down-Regulation
dc.subject.mesh	Mesenchymal Stem Cells
dc.subject.mesh	Mesenchymal Stem Cell Transplantation
dc.subject.mesh	Injections, Intra-Articular
dc.subject.mesh	Mesenchymal Stem Cells
dc.subject.mesh	Humans
dc.subject.mesh	Osteoarthritis
dc.subject.mesh	Interleukin-6
dc.subject.mesh	Mesenchymal Stem Cell Transplantation
dc.subject.mesh	Coculture Techniques
dc.subject.mesh	Injections, Intra-Articular
dc.subject.mesh	Down-Regulation
dc.subject.mesh	Humans
dc.subject.mesh	Coculture Techniques
dc.subject.mesh	Osteoarthritis
dc.subject.mesh	Interleukin-6
dc.subject.mesh	Down-Regulation
dc.subject.mesh	Mesenchymal Stem Cells
dc.subject.mesh	Mesenchymal Stem Cell Transplantation
dc.subject.mesh	Injections, Intra-Articular
dc.title	Understanding the effects of mesenchymal stromal cell therapy for treating osteoarthritis using an in vitro co-culture model.
dc.type	Journal Article
utslib.citation.volume	45
utslib.location.activity	United States
utslib.for	0601 Biochemistry and Cell Biology
utslib.for	0903 Biomedical Engineering
pubs.organisational-group	University of Technology Sydney
pubs.organisational-group	University of Technology Sydney/Faculty of Engineering and Information Technology
pubs.organisational-group	University of Technology Sydney/Faculty of Engineering and Information Technology/School of Biomedical Engineering
utslib.copyright.status	open_access	*
dc.date.updated	2024-04-29T08:09:44Z
pubs.publication-status	Published online
pubs.volume	45

Abstract:

Osteoarthritis (OA) is a leading cause of chronic pain and disability, for which there is no cure. Mesenchymal stromal cells (MSCs) have been used in clinical trials for treating OA due to their unique ability to generate paracrine anti-inflammatory and trophic signals. Interestingly, these studies have shown mainly short-term effects of MSCs in improving pain and joint function, rather than sustained and consistent benefits. This may reflect a change or loss in the therapeutic effects of MSCs after intra-articular injection. The present study aimed to unravel the reasons behind the variable efficacy of MSC injections for OA using an in vitro co-culture model. Osteoarthritic human synovial fibroblasts (OA-HSFs) were co-cultured with MSCs to investigate their reciprocal effects on cell responses and whether a short-term exposure of OA cells to MSCs was sufficient for reducing their diseased characteristics in a sustained manner. Gene expression and histological analyses were performed. OA-HSFs exposed to MSCs showed short-term downregulation of inflammatory markers. However, the MSCs showed upregulation of inflammatory markers and impaired ability to undergo osteogenesis and chondrogenesis in the presence of OA-HSFs. Moreover, short-term exposure of OA-HSFs to MSCs was found to be insufficient for inducing sustained changes to their diseased behaviour. These findings suggested that MSCs may not provide long-term effects in correcting the OA joint environment due to them adopting the diseased phenotype of the surrounding tissues, which has important implications for the future development of effective stem-cell-based OA treatments with long-term therapeutic efficacy.

Please use this identifier to cite or link to this item:

http://hdl.handle.net/10453/178466