World’s first transplant of cornea made from iPS cells

Main points

  • World’s first transplantation of corneal epithelial cell sheets made from human iPS cells
  • A new treatment for patients suffering from vision loss due to corneal disease


A group of researchers at the Graduate School of Medicine, Osaka University, led by Professor Kohji Nishida (Dept. of Ophthalmology), announced the transplantation of corneal epithelial cell sheets into a patient with corneal disease caused by a deficiency in corneal epithelial stem cells*1 on July 2019. The patient was discharged August 23, 2019, but is scheduled for regular post-operative observations.  

This is the world’s first clinical use of an induced pluripotent stem (iPS) cell*2 product to regenerate the cornea. The iPS cells were prepared at Kyoto University using donor cells from a third party. Nishida’s team then prepared the corneal epithelial cell sheets from the iPS cells using a differentiation protocol they established. The study’s primary goal is to test the safety of the transplanted cells.

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A loss of corneal epithelial stem cells can result in the cornea being covered by the conjunctiva. Transplantation is a standard treatment option, but the lack of donors or immune rejection limit the number of patients who benefit.

The use of iPS cells has the potential to resolve these issues. The Nishida group has been researching the application of iPS cells for corneal regeneration. In March 2019, the Ministry of Health, Labour and Welfare approved clinical research proposed by the group to transplant iPS cell-derived corneal epithelial cell sheets into patients with corneal disease.

Research plan

This project plans to treat 4 patients showing severe cases of corneal disease with iPS cell-derived corneal epithelial cell sheets. The first two paitents will be treated with an immunosuppressive, because the donor cells will not be HLA*3-matched. Following evaluation of these two patients, the condition of HLA-matching and immunosuppressant will be decided for the remaining two cases. The follow-up period for all operations is one year, followed by another one year follow-up survey.

The primary endpoint of the study is safety, and the secondary endpoints are visual acuity and corneal epithelial stem cell maintenance.

The patient who received the transplant in July is already undergoing follow-up observation. The second patient is scheduled to receive the transplant this calendar year.

Social significance

This study is investigating the First-in-Human regenerative medicine of the cornea using a transplant of iPS cell-derived corneal epithelial sheets. The use of iPS cells could overcome the two most limiting factors in this transplantation (donor shortage and graft rejection) and contribute to vision recovery in patients losing their sight due to corneal disease.


This research is funded by the Japan Agency for Medical Research and Development (AMED) “Network Program for the Realization of Regenerative Medicine, Highway for the Realization of Regenerative Medicine (iPS cells for cornea regeneration)” and “Practical Research in Regenerative Medicine (iPS cell-derived corneal epithelial cell sheets First-in-Human clinical research)”.


※1 Corneal epithelial stem cell loss
When damage to the eye from injury or disease causes an insufficient supply of corneal epithelial stem cells, the conjunctival epithelium can invade the cornea along with blood vessels to cover the cornea surface, resulting in visual impairment and possible blindness. Causes include burns, alkaline or acid exposure, Stevens-Johnson syndrome and ocular pemphigus.

※2 iPS (induced pluripotent stem) cells
iPS cells are somatic cells in which specific factors (reprogramming factors) caused the cells to convert into an embryonic state. Prof. Shinya Yamanaka, Kyoto University, reported the first iPS cells in 2006 (mouse) and first human iPS cells in 2007.

※3 HLA (human leukocyte antigens)
HLA are the product of major histocompatibility complexes with which the immune system can distinguish self and non-self cells. Identification as non-self by the immune system leads to rejection of a transplant.