A low dose cell therapy system for treating osteoarthritis: In vivo study and in vitro mechanistic investigations

Wang, B; Liu, W; Li, JJ; Chai, S; Xing, D; Yu, H; Zhang, Y; Yan, W; Xu, Z; Zhao, B; Du, Y; Jiang, Q

A low dose cell therapy system for treating osteoarthritis: In vivo study and in vitro mechanistic investigations

Wang, B Liu, W Li, JJ Chai, S Xing, D Yu, H Zhang, Y Yan, W Xu, Z Zhao, B Du, Y Jiang, Q

Permalink

Publisher:: Elsevier BV
Publication Type:: Journal Article
Citation:: Bioactive Materials, 2021
Issue Date:: 2021-06-01

Recently Added

	Filename	Description	Size
	1-s2.0-S2452199X21002498-main.pdf	Published version	8.97 MB	Adobe PDF	View/Open

Copyright Clearance Process

Recently Added
In Progress
Open Access

This item is new to OPUS and is not currently available.

Full metadata record

Field	Value	Language
dc.contributor.author	Wang, B
dc.contributor.author	Liu, W
dc.contributor.author	Li, JJ
dc.contributor.author	Chai, S
dc.contributor.author	Xing, D
dc.contributor.author	Yu, H
dc.contributor.author	Zhang, Y
dc.contributor.author	Yan, W
dc.contributor.author	Xu, Z
dc.contributor.author	Zhao, B
dc.contributor.author	Du, Y
dc.contributor.author	Jiang, Q
dc.date.accessioned	2021-07-27T07:12:21Z
dc.date.available	2021-07-27T07:12:21Z
dc.date.issued	2021-06-01
dc.identifier.citation	Bioactive Materials, 2021
dc.identifier.issn	2452-199X
dc.identifier.uri	http://hdl.handle.net/10453/149946
dc.description.abstract	Mesenchymal stem cells (MSCs) can be effective in alleviating the progression of osteoarthritis (OA). However, low MSC retention and survival at the injection site frequently require high doses of cells and/or repeated injections, which are not economically viable and create additional risks of complications. In this study, we produced MSC-laden microcarriers in spinner flask culture as cell delivery vehicles. These microcarriers containing a low initial dose of MSCs administered through a single injection in a rat anterior cruciate ligament (ACL) transection model of OA achieved similar reparative effects as repeated high doses of MSCs, as evaluated through imaging and histological analyses. Mechanistic investigations were conducted using a co-culture model involving human primary chondrocytes grown in monolayer, together with MSCs grown either within 3D constructs or as a monolayer. Co-culture supernatants subjected to secretome analysis showed significant decrease of inflammatory factors in the 3D group. RNA-seq of co-cultured MSCs and chondrocytes using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed processes relating to early chondrogenesis and increased extracellular matrix interactions in MSCs of the 3D group, as well as phenotypic maintenance in the co-cultured chondrocytes. The cell delivery platform we investigated may be effective in reducing the cell dose and injection frequency required for therapeutic applications.
dc.language	en
dc.publisher	Elsevier BV
dc.relation	http://purl.org/au-research/grants/nhmrc/1120249
dc.relation.ispartof	Bioactive Materials
dc.relation.isbasedon	10.1016/j.bioactmat.2021.05.029
dc.rights	info:eu-repo/semantics/restrictedAccess
dc.rights	This is an open access article under the CC
dc.title	A low dose cell therapy system for treating osteoarthritis: In vivo study and in vitro mechanistic investigations
dc.type	Journal Article
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	recently_added	*
dc.date.updated	2021-07-27T07:12:16Z
pubs.publication-status	Published

Abstract:

Mesenchymal stem cells (MSCs) can be effective in alleviating the progression of osteoarthritis (OA). However, low MSC retention and survival at the injection site frequently require high doses of cells and/or repeated injections, which are not economically viable and create additional risks of complications. In this study, we produced MSC-laden microcarriers in spinner flask culture as cell delivery vehicles. These microcarriers containing a low initial dose of MSCs administered through a single injection in a rat anterior cruciate ligament (ACL) transection model of OA achieved similar reparative effects as repeated high doses of MSCs, as evaluated through imaging and histological analyses. Mechanistic investigations were conducted using a co-culture model involving human primary chondrocytes grown in monolayer, together with MSCs grown either within 3D constructs or as a monolayer. Co-culture supernatants subjected to secretome analysis showed significant decrease of inflammatory factors in the 3D group. RNA-seq of co-cultured MSCs and chondrocytes using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed processes relating to early chondrogenesis and increased extracellular matrix interactions in MSCs of the 3D group, as well as phenotypic maintenance in the co-cultured chondrocytes. The cell delivery platform we investigated may be effective in reducing the cell dose and injection frequency required for therapeutic applications.

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

http://hdl.handle.net/10453/149946