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

Research output: Contribution to journalArticlepeer-review

44 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)1097-1108
Number of pages12
JournalStem Cells and Development
Issue number16
Publication statusPublished - 2018 Aug 15


  • cornea
  • corneal endothelium
  • mesenchymal stem cells
  • neural crest
  • umbilical cord

ASJC Scopus subject areas

  • Hematology
  • Developmental Biology
  • Cell Biology


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