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Mechanical stress potentiates the differentiation of periodontal ligament stem cells into keratocytes
Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
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2018 (English)In: British Journal of Ophthalmology, ISSN 0007-1161, E-ISSN 1468-2079, Vol. 102, no 4, p. 562-569Article in journal (Refereed) Published
Abstract [en]

Aims To explore the role of corneal-shaped static mechanical strain on the differentiation of human periodontal ligament stem cells (PDLSCs) into keratocytes and the possible synergistic effects of mechanics and inducing medium. Methods PDLSCs were exposed to 3% static dome-shaped mechanical strain in a Flexcell Tension System for 3 days and 7 days. Keratocyte phenotype was determined by gene expression of keratocyte markers. Keratocyte differentiation (inducing) medium was introduced in the Flexcell system, either continuously or intermittently combined with mechanical stimulation. The synergistic effects of mechanics and inducing medium on keratocyte differentiation was evaluated by gene and protein expression of keratocyte markers. Finally, a multilamellar cell sheet was assembled by seeding PDLSCs on a collagen membrane and inducing keratocyte differentiation. The transparency of the cell sheet was assessed, and typical markers of native human corneal stroma were evaluated by immunofluorescence staining. Results Dome-shaped mechanical stimulation promoted PDLSCs to differentiate into keratocytes, as shown by the upregulation of ALDH3A1, CD34, LUM, COL I and COL V. The expression of integrins were also upregulated after mechanical stimulation, including integrin alpha 1, alpha 2, beta 1 and non-muscle myosin II B. A synergistic effect of mechanics and inducing medium was found on keratocyte differentiation. The cell sheets were assembled under the treatment of mechanics and inducing medium simultaneously. The cell sheets were transparent, multilamellar and expressed typical markers of corneal stroma. Conclusion Dome-shaped mechanical stimulation promotes differentiation of PDLSCs into keratocytes and has synergistic effects with inducing medium. Multilamellar cell sheets that resemble native human corneal stroma show potential for future clinical applications.

Place, publisher, year, edition, pages
BMJ Publishing Group Ltd, 2018. Vol. 102, no 4, p. 562-569
Keywords [en]
PDLSCs, corneal stroma, mechanics, inducing medium, differentiation, cell-sheet
National Category
Ophthalmology
Identifiers
URN: urn:nbn:se:umu:diva-147334DOI: 10.1136/bjophthalmol-2017-311150ISI: 000429732500026PubMedID: 29306866OAI: oai:DiVA.org:umu-147334DiVA, id: diva2:1206658
Available from: 2018-05-17 Created: 2018-05-17 Last updated: 2018-06-09Bibliographically approved

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Chen, JialinZhang, WeiBackman, Ludvig J.Kelk, PeymanDanielson, Patrik

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