Self-assembly of gelatin microcarrier-based MSC microtissues for spinal cord injury repair

Liu, H; Yan, X; Jiu, J; Li, JJ; Zhang, Y; Wang, G; Li, D; Yan, L; Du, Y; Zhao, B; Wang, B

Self-assembly of gelatin microcarrier-based MSC microtissues for spinal cord injury repair

Liu, H Yan, X Jiu, J Li, JJ Zhang, Y Wang, G Li, D Yan, L Du, Y Zhao, B Wang, B

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Publisher:: ELSEVIER SCIENCE SA
Publication Type:: Journal Article
Citation:: Chemical Engineering Journal, 2023, 451
Issue Date:: 2023-01-01

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Field	Value	Language
dc.contributor.author	Liu, H
dc.contributor.author	Yan, X
dc.contributor.author	Jiu, J
dc.contributor.author	Li, JJ
dc.contributor.author	Zhang, Y
dc.contributor.author	Wang, G
dc.contributor.author	Li, D
dc.contributor.author	Yan, L
dc.contributor.author	Du, Y
dc.contributor.author	Zhao, B
dc.contributor.author	Wang, B
dc.date.accessioned	2023-01-18T05:14:04Z
dc.date.available	2023-01-18T05:14:04Z
dc.date.issued	2023-01-01
dc.identifier.citation	Chemical Engineering Journal, 2023, 451
dc.identifier.issn	1385-8947
dc.identifier.issn	1873-3212
dc.identifier.uri	http://hdl.handle.net/10453/165122
dc.description.abstract	Current approaches for treating spinal cord injury (SCI) are mainly based on cell transplantation. Mesenchymal stem cells (MSCs) can help slow the progression of SCI due to their trophic function. However, SCI creates a complex microenvironment that reduces cell activity and hence cellular function, ultimately resulting in poor therapeutic outcomes. To help maintain function in transplanted cells, we produced functional tissue constructs by self-assembly of MSC microtissues comprising of porous gelatin microcarriers (GM) and MSCs. These microtissues maintained cellular activity without incurring an excessive amount of apoptosis and delayed senescence in vitro. The paracrine function of MSCs also improved within microtissues, shown by the increased secretion of nerve regeneration-related factors. Microtissues were transplanted in a rat model of complete spinal cord transection, and therapeutic effects were evaluated through behavioral measurements, imaging, histology, and western blot analysis. RNA-seq of spinal cord tissues using Gene Ontology analysis further revealed that the microtissues may have induced repair in SCI through mechanisms related to neurotrophin-3 (NT-3) regulation of response mediator protein 2 (CRMP2) phosphorylation, and inhibition of inflammatory response through interleukin-17 (IL-17), Chemokine C-X-C motif Ligand 1 (CXCL1) axis. The gelatin microcarrier-based MSC microtissues we developed may be effective in providing a new treatment strategy for SCI.
dc.language	English
dc.publisher	ELSEVIER SCIENCE SA
dc.relation	http://purl.org/au-research/grants/nhmrc/1120249
dc.relation.ispartof	Chemical Engineering Journal
dc.relation.isbasedon	10.1016/j.cej.2022.138806
dc.rights	info:eu-repo/semantics/closedAccess
dc.subject	0904 Chemical Engineering, 0905 Civil Engineering, 0907 Environmental Engineering
dc.subject.classification	Chemical Engineering
dc.title	Self-assembly of gelatin microcarrier-based MSC microtissues for spinal cord injury repair
dc.type	Journal Article
utslib.citation.volume	451
utslib.for	0904 Chemical Engineering
utslib.for	0905 Civil Engineering
utslib.for	0907 Environmental 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	closed_access	*
dc.date.updated	2023-01-18T05:13:55Z
pubs.publication-status	Published
pubs.volume	451

Abstract:

Current approaches for treating spinal cord injury (SCI) are mainly based on cell transplantation. Mesenchymal stem cells (MSCs) can help slow the progression of SCI due to their trophic function. However, SCI creates a complex microenvironment that reduces cell activity and hence cellular function, ultimately resulting in poor therapeutic outcomes. To help maintain function in transplanted cells, we produced functional tissue constructs by self-assembly of MSC microtissues comprising of porous gelatin microcarriers (GM) and MSCs. These microtissues maintained cellular activity without incurring an excessive amount of apoptosis and delayed senescence in vitro. The paracrine function of MSCs also improved within microtissues, shown by the increased secretion of nerve regeneration-related factors. Microtissues were transplanted in a rat model of complete spinal cord transection, and therapeutic effects were evaluated through behavioral measurements, imaging, histology, and western blot analysis. RNA-seq of spinal cord tissues using Gene Ontology analysis further revealed that the microtissues may have induced repair in SCI through mechanisms related to neurotrophin-3 (NT-3) regulation of response mediator protein 2 (CRMP2) phosphorylation, and inhibition of inflammatory response through interleukin-17 (IL-17), Chemokine C-X-C motif Ligand 1 (CXCL1) axis. The gelatin microcarrier-based MSC microtissues we developed may be effective in providing a new treatment strategy for SCI.

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http://hdl.handle.net/10453/165122