Laminin-511 and -521-based matrices for efficient ex vivo-expansion of human limbal epithelial progenitor cells

Polisetti N, Sorokin L, Okumura N, Koizumi N, Kinoshita S, Kruse F, Schlötzer-Schrehardt U (2017)

Publication Type: Journal article

Publication year: 2017

Journal

Scientific Reports Nature Publishing Group: Open Access Journals - Option B

Book Volume: 7

Pages Range: 5152

Journal Issue: 1

DOI: 10.1038/s41598-017-04916-x

Abstract

Optimization of culture conditions for human limbal epithelial stem/progenitor cells (LEPC) that incorporate the in vivo cell-matrix interactions are essential to enhance LEPC ex vivo-expansion and transplantation efficiency. Here, we investigate the efficacy of laminin (LN) isoforms preferentially expressed in the limbal niche as culture matrices for epithelial tissue engineering. Analyses of expression patterns of LN chains in the human limbal niche provided evidence for enrichment of LN-?2, -?3, -?5, -?1, -?2, -?3, -?1, -?2 and -?3 chains in the limbal basement membrane, with LN-?5 representing a signature component specifically produced by epithelial progenitor cells. Recombinant human LN-521 and LN-511 significantly enhanced in vitro LEPC adhesion, migration and proliferation compared to other isoforms, and maintained phenotype stability. The bioactive LN-511-E8 fragment carrying only C-terminal domains showed similar efficacy as full-length LN-511. Functional blocking of ?3?1 and ?6?1 integrins suppressed adhesion of LEPC to LN-511/521-coated surfaces. Cultivation of LEPC on fibrin-based hydrogels incorporating LN-511-E8 resulted in firm integrin-mediated adhesion to the scaffold and well-stratified epithelial constructs, with maintenance of a progenitor cell phenotype in their (supra)basal layers. Thus, the incorporation of chemically defined LN-511-E8 into biosynthetic scaffolds represents a promising approach for xeno-free corneal epithelial tissue engineering for ocular surface reconstruction.

Authors with CRIS profile

Friedrich Kruse Lehrstuhl für Augenheilkunde Ursula Schlötzer-Schrehardt Medizinische Fakultät

Involved external institutions

Kyoto Prefectural University of Medicine / 京都府立医科大学 JP Japan (JP) Doshisha University / 同志社大学 JP Japan (JP) Westfälische Wilhelms-Universität (WWU) Münster DE Germany (DE)

How to cite

APA:

Polisetti, N., Sorokin, L., Okumura, N., Koizumi, N., Kinoshita, S., Kruse, F., & Schlötzer-Schrehardt, U. (2017). Laminin-511 and -521-based matrices for efficient ex vivo-expansion of human limbal epithelial progenitor cells. Scientific Reports, 7(1), 5152. https://doi.org/10.1038/s41598-017-04916-x

MLA:

Polisetti, Naresh, et al. "Laminin-511 and -521-based matrices for efficient ex vivo-expansion of human limbal epithelial progenitor cells." Scientific Reports 7.1 (2017): 5152.

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