Corneal regeneration by conditioned medium of human uterine cervical stem cells is mediated by TIMP-1 and TIMP-2

Autor: Juan Sendon-Lago, María Bermúdez, Francisco Gonzalez, Noemi Eiro, Roman Perez-Fernandez, Francisco J. Vizoso, Anxo Martinez-Ordoñez, Samuel Seoane, Jorge Saa
Rok vydání: 2018
Předmět:
0301 basic medicine
Atropine
Male
genetic structures
Blotting
Western
Apoptosis
Cervix Uteri
Real-Time Polymerase Chain Reaction
Proinflammatory cytokine
Andrology
Rats
Sprague-Dawley
03 medical and health sciences
Cellular and Molecular Neuroscience
0302 clinical medicine
Cell Movement
Tandem Mass Spectrometry
Cornea
medicine
Animals
Regeneration
Sodium Hydroxide
Cell Proliferation
Tissue Inhibitor of Metalloproteinase-2
Wound Healing
Tissue Inhibitor of Metalloproteinase-1
Chemistry
Cell growth
Regeneration (biology)
Stem Cells
Epithelium
Corneal
Cell migration
eye diseases
Sensory Systems
Rats
Ophthalmology
Disease Models
Animal
030104 developmental biology
medicine.anatomical_structure
Ki-67 Antigen
Culture Media
Conditioned
030221 ophthalmology & optometry
Cytokines
Dry Eye Syndromes
Female
sense organs
Rabbits
Stem cell
Immunostaining
Zdroj: Experimental eye research. 180
ISSN: 1096-0007
Popis: The aim of the present study was to evaluate the effect and the mechanism of action of the conditioned medium from human uterine cervical stem cells (CM-hUCESC) on corneal wound healing in a rabbit dry eye model. To do this, dry eye and corneal epithelial injuries were induced in rabbits by topical administration of atropine sulfate and NaOH. Hematoxylin-Eosin (H&E) and Ki-67 immunostaining were carried out to evaluate corneal damage and cell proliferation, and real-time PCR was used to evaluate proinflammatory cytokines in the cornea. In addition, in order to investigate possible factors involved in corneal regeneration, primary cultures of rat corneal epithelial cells (rCECs) were used to evaluate cell migration, proliferation, and apoptosis before and after immunoprecipitation of specific factors from the CM-hUCESC. Results showed that CM-hUCESC treatment significantly improved epithelial regeneration in rabbits with dry eye induced by atropine and reduced corneal pro-inflammatory TNF-α, MCP-1, MIP-1α and IL-6 cytokines. In addition, metalloproteinase inhibitors TIMP-1 and TIMP-2, which are present at high levels in CM-hUCESC, mediated corneal regenerative effects by both inducing corneal epithelial cell proliferation and inhibiting apoptosis. In summary, CM-hUCESC induces faster corneal regeneration in a rabbit model of dry eye induced by atropine than conventional treatments, being TIMP-1 and TIMP-2 mediators in this process. The results indicate that an alternative CM-based treatment for some corneal conditions is achievable, although future studies would be necessary to investigate other factors involved in the multiple observed effects of CM-hUCESC.
Databáze: OpenAIRE
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