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
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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