Tunable hydrogels for mesenchymal stem cell delivery: Integrin-induced transcriptome alterations and hydrogel optimization for human wound healing.
Chemokine
Cytokines
Differentiation
Gene expression
Integrins
Mesenchymal stem cells (MSCs)
Stem cell culture
Tissue regeneration
Journal
Stem cells (Dayton, Ohio)
ISSN: 1549-4918
Titre abrégé: Stem Cells
Pays: England
ID NLM: 9304532
Informations de publication
Date de publication:
02 2020
02 2020
Historique:
received:
03
05
2018
revised:
08
09
2019
accepted:
18
09
2019
pubmed:
28
10
2019
medline:
15
12
2020
entrez:
25
10
2019
Statut:
ppublish
Résumé
Therapeutic applications for mesenchymal stem/stromal cells (MSCs) are growing; however, the successful implementation of these therapies requires the development of appropriate MSC delivery systems. Hydrogels are ideally suited to cultivate MSCs but tuning hydrogel properties to match their specific in vivo applications remains a challenge. Thus, further characterization of how hydrogel-based delivery vehicles broadly influence MSC function and fate will help lead to the next generation of more intelligently designed delivery vehicles. To date, few attempts have been made to comprehensively characterize hydrogel impact on the MSC transcriptome. Herein, we have synthesized cell-degradable hydrogels based on bio-inert poly(ethylene glycol) tethered with specific integrin-binding small molecules and have characterized their resulting effect on the MSC transcriptome when compared with 2D cultured and untethered 3D hydrogel cultured MSCs. The 3D culture systems resulted in alterations in the MSC transcriptome, as is evident by the differential expression of genes related to extracellular matrix production, glycosylation, metabolism, signal transduction, gene epigenetic regulation, and development. For example, genes important for osteogenic differentiation were upregulated in 3D hydrogel cultures, and the expression of these genes could be partially suppressed by tethering an integrin-binding RGD peptide within the hydrogel. Highlighting the utility of tunable hydrogels, when applied to ex vivo human wounds the RGD-tethered hydrogel was able to support wound re-epithelialization, possibly due to its ability to increase PDGF expression and decrease IL-6 expression. These results will aid in future hydrogel design for a broad range of applications.
Substances chimiques
Hydrogels
0
Integrins
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
231-245Subventions
Organisme : NIH Transformative Grant
ID : 1R01GM099688
Pays : International
Informations de copyright
©AlphaMed Press 2019.
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