Corneal Epithelial Wound Healing and Bactericidal Effect of Conditioned Medium From Human Uterine Cervical Stem Cells

被引：76

作者：

Bermudez, Maria A. ^{[1
]}

Sendon-Lago, Juan ^{[2
]}

Eiro, Noemi ^{[3
,4
]}

Trevino, Mercedes ^{[5
]}

Gonzalez, Francisco ^{[1
,6
]}

Yebra-Pimentel, Eva ^{[7
]}

Jesus Giraldez, Maria ^{[7
]}

Macia, Manuel ^{[8
]}

Luz Lamelas, Maria ^{[3
]}

Saa, Jorge ^{[3
,9
]}

Vizoso, Francisco ^{[3
,4
]}

Perez-Fernandez, Roman ^{[2
]}

机构：

[1] Univ Santiago de Compostela, Ctr Res Mol Med & Chron Dis CIMUS, Dept Surg, Santiago De Compostela, Spain

[2] Univ Santiago de Compostela, Ctr Res Mol Med & Chron Dis CIMUS, Dept Phys, Santiago De Compostela, Spain

[3] Fdn Hosp Jove, Unidad Invest, Gijon 33290, Asturias, Spain

[4] Fdn Invest Celulas Madre Uterinas FICEMU, Gijon, Spain

[5] Univ Santiago de Compostela, Complejo Hosp, Microbiol Serv, Santiago De Compostela, Spain

[6] Univ Santiago de Compostela, Complejo Hosp, Serv Ophthalmol, Santiago De Compostela, Spain

[7] Univ Santiago de Compostela, Opt & Optometry Fac, Optometry Area, Dept Appl Phys, Santiago De Compostela, Spain

[8] Univ Santiago de Compostela, Dept Obstet & Gynecol, Santiago De Compostela, Spain

[9] Fdn Hosp Jove, Serv Ophthalmol, Gijon, Spain

来源：

INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE | 2015年 / 56卷 / 02期

关键词：

dry eye; corneal ulcers; E; coli; S; epiderimidis; secretoma; LACRIMAL GLAND; PSYCHOLOGICAL STRESS; MOUSE MODEL; IN-VITRO; EXPRESSION; GROWTH; ANTIBACTERIAL; TRANSPLANTATION; IDENTIFICATION; INDUCTION;

D O I：

10.1167/iovs.14-15859

中图分类号：

R77 [眼科学];

学科分类号：

100212 ;

摘要：

PURPOSE. To evaluate the effect of conditioned medium from human uterine cervical stem cells (CM-hUCESCs) on corneal epithelial healing in a rat model of dry eye after alkaline corneal epithelial ulcer. We also tested the bactericidal effect of CM-hUCESCs. METHODS. Dry eye was induced in rats by extraocular lacrimal gland excision, and corneal ulcers were produced using NaOH. Corneal histologic evaluation was made with hematoxylin-eosin (H&E) staining. Real-time PCR was used to evaluate mRNA expression levels of proinflammatory cytokines. We also studied the bactericidal effect of CM-hUCESCs in vitro and on infected corneal contact lenses (CLs) using Escherichia coli and Staphylococcus epidermidis bacteria. In addition, in order to investigate proteins from CM-hUCESCs that could mediate these effects, we carried out a human cytokine antibody array. RESULTS. After injury, dry eyes treated with CM-hUCESCs significantly improved epithelial regeneration and showed reduced corneal macrophage inflammatory protein-1 alpha (MIP-1 alpha) and TNF-alpha mRNA expression as compared to untreated eyes and eyes treated with culture medium or sodium hyaluronate ophthalmic drops. In addition, we found in CM-hUCESCs high levels of proteins, such as tissue inhibitors of metalloproteinases 1 and 2, fibroblast growth factor 6 and 7, urokinase receptor, and hepatocyte growth factor, that could mediate these effects. In vitro, CM-hUCESCs showed a clear bactericidal effect on both E. coli and S. epidermidis and CLs infected with S. epidermidis. Analyses of CM-hUCESCs showed elevated levels of proteins that could be involved in the bactericidal effect, such as the chemokine (C-X-C motif) ligands 1, 6, 8, 10, and the chemokine (C-C motif) ligands 5 and 20. CONCLUSIONS. Treatment with CM-hUCESCs improved wound healing of alkali-injured corneas and showed a strong bactericidal effect on CLs. Patients using CLs and suffering from dry eye, allergies induced by commercial solutions, or small corneal injuries could benefit from this treatment.

引用

页码：983 / 992

页数：10

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