Corneal Endothelial Regeneration Using Mesenchymal Stem Cells Derived from Human Umbilical Cord
Autor: | Akiko Ogawa, Kazunari Higa, Hideyuki Miyashita, Kazuya Yamashita, Shigeto Shimmura, Shin Hatou, Emi Inagaki, Kazuo Tsubota |
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Rok vydání: | 2018 |
Předmět: |
0301 basic medicine
Corneal endothelium Pathology medicine.medical_specialty genetic structures medicine.medical_treatment Biology Mesenchymal Stem Cell Transplantation Umbilical cord Umbilical Cord Cornea Corneal Transplantation 03 medical and health sciences medicine Animals Humans Regeneration Transplantation Homologous Corneal transplantation Corneal Dystrophies Hereditary Homeodomain Proteins Glycogen Synthase Kinase 3 beta Tissue Engineering Tight junction Endothelium Corneal Mesenchymal stem cell Endothelial Cells Neural crest Cell Differentiation Mesenchymal Stem Cells Cell Biology Hematology eye diseases 030104 developmental biology medicine.anatomical_structure Zonula Occludens-1 Protein Bullous keratopathy Rabbits sense organs Sodium-Potassium-Exchanging ATPase Transcription Factors Developmental Biology |
Zdroj: | Stem Cells and Development. 27:1097-1108 |
ISSN: | 1557-8534 1547-3287 |
Popis: | Corneal blindness is the third leading cause of blindness in the world, and one of the main etiologies is dysfunction of the corneal endothelium. Current treatment of corneal endothelial disease is allogenic corneal transplantation, which is limited by the global shortage of donor corneas and immunological rejection. The corneal endothelium consists of a monolayer of cells derived from the neural crest and mesoderm. Its main function is to prevent corneal edema by tight junctions formed by zonular occludens-1 (ZO-1) and Na, K-ATPase pump function. The human umbilical cord (UC) is a rich source of mesenchymal stem cells (MSCs). UC-MSCs that have multi-lineage potential may be an accessible allogenic source. After inducing differentiation with medium containing glycogen synthase kinase (GSK) 3-β inhibitor, UC-MSCs formed polygonal corneal endothelial-like cells that functioned as tissue-engineered corneal endothelium (UTECE). Expressions of major corneal endothelial markers were confirmed by reverse transcription-polymerase chain reaction (RT-PCR) and quantitative RT-PCR (qRT-PCR). Western blotting confirmed the expression of Na,K-ATPase and PITX2, the functional and developmental markers of corneal endothelial cells. Immunohistochemistry revealed the localization of Na,K-ATPase and ZO-1 in cell-cell junctions, suggesting the presence of tight junctions. In vitro functional analysis revealed that UTECE had significantly high pump function compared with UC-MSCs. Moreover, UTECE transplanted into a rabbit model of bullous keratopathy successfully maintained corneal thickness and transparency. Our findings suggest that UTECE may be used as a source of allogenic cells for the treatment of corneal endothelial disease. |
Databáze: | OpenAIRE |
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