Paracrine Activity from Adipose-Derived Stem Cells on In Vitro Wound Healing in Human Tympanic Membrane Keratinocytes

Ong, Huan TingEar Sci Inst Australia, Nedlands, WA, Australia.;Murdoch Univ, Sch Vet & Life Sci, Murdoch, WA, Australia. (author)

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.

Redmond, Sharon L.Ear Sci Inst Australia, Nedlands, WA, Australia.;Univ Western Australia, Ear Sci Ctr, Perth, WA, Australia. (author)
Marano, Robert J.Ear Sci Inst Australia, Nedlands, WA, Australia.;Univ Western Australia, Ear Sci Ctr, Perth, WA, Australia. (author)
Atlas, Marcus D.Ear Sci Inst Australia, Nedlands, WA, Australia.;Univ Western Australia, Ear Sci Ctr, Perth, WA, Australia. (author)
von Unge, MagnusUppsala universitet,Centrum för klinisk forskning, Västerås,Akershus Univ Hosp, Div Surg, Oslo, Norway.;Univ Oslo, Oslo, Norway.(Swepub:uu)magvo551 (author)
Aabel, PederAkershus Univ Hosp, Div Surg, Oslo, Norway.;Univ Oslo, Oslo, Norway. (author)
Dilley, Rodney J.Ear Sci Inst Australia, Nedlands, WA, Australia.;Univ Western Australia, Ear Sci Ctr, Perth, WA, Australia.;Univ Western Australia, Ctr Cell Therapy & Regenerat Med, Perth, WA, Australia. (author)
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. (creator_code:org_t)

In:Stem Cells and Development: MARY ANN LIEBERT, INC26:6, s. 405-4181547-32871557-8534

By the author/editor: Ong, Huan Ting; Redmond, Sharon ...; Marano, Robert J ...; Atlas, Marcus D.; von Unge, Magnus; Aabel, Peder; show more...; Dilley, Rodney J ...; show less...

About the subject

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Basic Medicine; and Cell and Molecul ...

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...; and Hematology

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