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Paracrine Activity from Adipose-Derived Stem Cells on In Vitro Wound Healing in Human Tympanic Membrane Keratinocytes
Ear Sci Inst Australia, Nedlands, WA, Australia.;Murdoch Univ, Sch Vet & Life Sci, Murdoch, WA, Australia..
Ear Sci Inst Australia, Nedlands, WA, Australia.;Univ Western Australia, Ear Sci Ctr, Perth, WA, Australia..
Ear Sci Inst Australia, Nedlands, WA, Australia.;Univ Western Australia, Ear Sci Ctr, Perth, WA, Australia..
Ear Sci Inst Australia, Nedlands, WA, Australia.;Univ Western Australia, Ear Sci Ctr, Perth, WA, Australia..
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2017 (English)In: Stem Cells and Development, ISSN 1547-3287, E-ISSN 1557-8534, Vol. 26, no 6, p. 405-418Article in journal (Refereed) Published
Abstract [en]

Stem cell therapies for tympanic membrane repair have shown initial experimental success using mesenchymal stem cells in rat models to promote healing; however, the mechanisms providing this benefit are not known. We investigated in vitro the paracrine effects of human adipose-derived stem cells (ADSCs) on wound healing mechanisms for human tympanic membrane-derived keratinocytes (hTM) and immortalized human keratinocytes (HaCaT). ADSC conditioned media (CMADSC) were assessed for paracrine activity on keratinocyte proliferation and migration, with hypoxic conditions for ADSC culture used to generate contrasting effects on cytokine gene expression. Keratinocytes cultured in CMADSC showed a significant increase in cell number compared to serum-free cultures and further significant increases in hypoxic CMADSC. Assessment of ADSC gene expression on a cytokine array showed a range of wound healing cytokines expressed and under stringent hypoxic and serum-free conditions was upregulated (VEGF A, MMP9, Tissue Factor, PAI-1) or downregulated (CXCL5, CCL7, TNF-). Several of these may contribute to the activity of conditioned media on the keratinocytes with potential applications in TM perforation repair. VEGFA protein was confirmed by immunoassay to be increased in conditioned media. Together with gene regulation associated with hypoxia in ADSCs, this study has provided several strong leads for a stem cell-derived approach to TM wound healing.

Place, publisher, year, edition, pages
MARY ANN LIEBERT, INC , 2017. Vol. 26, no 6, p. 405-418
Keywords [en]
gene expression, growth factors, MSC, wound healing
National Category
Cell and Molecular Biology Hematology
Identifiers
URN: urn:nbn:se:uu:diva-320928DOI: 10.1089/scd.2016.0204ISI: 000395585600003PubMedID: 28052725OAI: oai:DiVA.org:uu-320928DiVA, id: diva2:1091604
Available from: 2017-04-27 Created: 2017-04-27 Last updated: 2018-01-13Bibliographically approved

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von Unge, Magnus

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