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Topical administration of orbital fat-derived stem cells promotes corneal tissue regeneration.
Stem Cell Res Ther. 2013 Jun 14; 4(3):72.SC

Abstract

INTRODUCTION

Topical administration of eye drops is the major route for drug delivery to the cornea. Orbital fat-derived stem cells (OFSCs) possess an in vitro corneal epithelial differentiation capacity. Both the safety and immunomodulatory ability of systemic OFSC transplantation were demonstrated in our previous work. In this study, we investigated the safety, therapeutic effect, and mechanism(s) of topical OFSC administration in an extensive alkali-induced corneal wound.

METHODS

Corneal injury was created by contact of a piece of 0.5 N NaOH-containing filter paper on the corneal surface of a male Balb/c mouse for 30 s. The area of the filter paper covered the central 70% or 100% of the corneal surface. OFSCs (2 × 10(5)) in 5 μl phosphate-buffered saline (PBS) were given by topical administration (T) twice a day or by two intralimbal (IL) injections in the right cornea, while 5 μl of PBS in the left cornea served as the control.

RESULTS

Topical OFSCs promoted corneal re-epithelialization of both the limbal-sparing and limbal-involved corneal wounds. In the first three days, topical OFSCs significantly reduced alkali-induced corneal edema and stromal infiltration according to a histopathological examination. Immunohistochemistry and immunofluorescence staining revealed that transplanted cells were easily detectable in the corneal epithelium, limbal epithelium and stroma, but only some of transplanted cells at the limbal epithelium had differentiated into cytokeratin 3-expressing cells. OFSCs did not alter neutrophil (Ly6G) levels in the cornea, but significantly reduced macrophage (CD68) infiltration and inducible nitrous oxide synthetase (iNOS) production during acute corneal injury as quantified by a Western blot analysis. Continuous topical administration of OFSCs for seven days improved corneal transparency, and this was accompanied by diffuse stromal engraftment of transplanted cells and differentiation into p63-expressing cells at the limbal area. The therapeutic effect of the topical administration of OFSCs was superior to that of the IL injection. OFSCs from the IL injection clustered in the limbal area and central corneal epithelium, which was associated with a persistent corneal haze.

CONCLUSIONS

Topical OFSC administration is a simple, non-surgical route for stem cell delivery to promote corneal tissue regeneration through ameliorating acute inflammation and corneal epithelial differentiation. The limbal area serves as a niche for OFSCs differentiating into corneal epithelial cells in the first week, while the stroma is a potential site for anti-inflammation of OFSCs. Inhibition of corneal inflammation is related to corneal transparency.

Authors

No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23769140

Citation

Lin, Ko-Jo, et al. "Topical Administration of Orbital Fat-derived Stem Cells Promotes Corneal Tissue Regeneration." Stem Cell Research & Therapy, vol. 4, no. 3, 2013, p. 72.
Lin KJ, Loi MX, Lien GS, et al. Topical administration of orbital fat-derived stem cells promotes corneal tissue regeneration. Stem Cell Res Ther. 2013;4(3):72.
Lin, K. J., Loi, M. X., Lien, G. S., Cheng, C. F., Pao, H. Y., Chang, Y. C., Ji, A. T., & Ho, J. H. (2013). Topical administration of orbital fat-derived stem cells promotes corneal tissue regeneration. Stem Cell Research & Therapy, 4(3), 72. https://doi.org/10.1186/scrt223
Lin KJ, et al. Topical Administration of Orbital Fat-derived Stem Cells Promotes Corneal Tissue Regeneration. Stem Cell Res Ther. 2013 Jun 14;4(3):72. PubMed PMID: 23769140.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Topical administration of orbital fat-derived stem cells promotes corneal tissue regeneration. AU - Lin,Ko-Jo, AU - Loi,Mei-Xue, AU - Lien,Gi-Shih, AU - Cheng,Chieh-Feng, AU - Pao,Hsiang-Yin, AU - Chang,Yun-Chuang, AU - Ji,Andrea Tung-Qian, AU - Ho,Jennifer Hui-Chun, Y1 - 2013/06/14/ PY - 2012/12/31/received PY - 2013/05/20/accepted PY - 2013/6/18/entrez PY - 2013/6/19/pubmed PY - 2015/3/31/medline SP - 72 EP - 72 JF - Stem cell research & therapy JO - Stem Cell Res Ther VL - 4 IS - 3 N2 - INTRODUCTION: Topical administration of eye drops is the major route for drug delivery to the cornea. Orbital fat-derived stem cells (OFSCs) possess an in vitro corneal epithelial differentiation capacity. Both the safety and immunomodulatory ability of systemic OFSC transplantation were demonstrated in our previous work. In this study, we investigated the safety, therapeutic effect, and mechanism(s) of topical OFSC administration in an extensive alkali-induced corneal wound. METHODS: Corneal injury was created by contact of a piece of 0.5 N NaOH-containing filter paper on the corneal surface of a male Balb/c mouse for 30 s. The area of the filter paper covered the central 70% or 100% of the corneal surface. OFSCs (2 × 10(5)) in 5 μl phosphate-buffered saline (PBS) were given by topical administration (T) twice a day or by two intralimbal (IL) injections in the right cornea, while 5 μl of PBS in the left cornea served as the control. RESULTS: Topical OFSCs promoted corneal re-epithelialization of both the limbal-sparing and limbal-involved corneal wounds. In the first three days, topical OFSCs significantly reduced alkali-induced corneal edema and stromal infiltration according to a histopathological examination. Immunohistochemistry and immunofluorescence staining revealed that transplanted cells were easily detectable in the corneal epithelium, limbal epithelium and stroma, but only some of transplanted cells at the limbal epithelium had differentiated into cytokeratin 3-expressing cells. OFSCs did not alter neutrophil (Ly6G) levels in the cornea, but significantly reduced macrophage (CD68) infiltration and inducible nitrous oxide synthetase (iNOS) production during acute corneal injury as quantified by a Western blot analysis. Continuous topical administration of OFSCs for seven days improved corneal transparency, and this was accompanied by diffuse stromal engraftment of transplanted cells and differentiation into p63-expressing cells at the limbal area. The therapeutic effect of the topical administration of OFSCs was superior to that of the IL injection. OFSCs from the IL injection clustered in the limbal area and central corneal epithelium, which was associated with a persistent corneal haze. CONCLUSIONS: Topical OFSC administration is a simple, non-surgical route for stem cell delivery to promote corneal tissue regeneration through ameliorating acute inflammation and corneal epithelial differentiation. The limbal area serves as a niche for OFSCs differentiating into corneal epithelial cells in the first week, while the stroma is a potential site for anti-inflammation of OFSCs. Inhibition of corneal inflammation is related to corneal transparency. SN - 1757-6512 UR - https://www.unboundmedicine.com/medline/citation/23769140/Topical_administration_of_orbital_fat_derived_stem_cells_promotes_corneal_tissue_regeneration_ L2 - https://stemcellres.biomedcentral.com/articles/10.1186/scrt223 DB - PRIME DP - Unbound Medicine ER -