Corneal Endothelial Regeneration Using Mesenchymal Stem Cells Derived from Human Umbilical Cord

Kazuya Yamashita, Emi Inagaki, Shin Hatou, Kazunari Higa, Akiko Ogawa, Hideyuki Miyashita, Kazuo Tsubota, Shigeto Shimmura

研究成果: ジャーナルへの寄稿学術論文査読

44 被引用数 (Scopus)

抄録

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.

本文言語英語
ページ(範囲)1097-1108
ページ数12
ジャーナルStem Cells and Development
27
16
DOI
出版ステータス出版済み - 15-08-2018
外部発表はい

All Science Journal Classification (ASJC) codes

  • 血液学
  • 発生生物学
  • 細胞生物学

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