Abstract
The corneal endothelium is essential for maintaining corneal transparency; therefore, corneal endothelial dysfunction causes serious vision loss. Tissue engineering-based therapy is potentially a less invasive and more effective therapeutic modality. We recently started a first-in-man clinical trial of cell-based therapy for treating corneal endothelial dysfunction in Japan. However, the senescence of corneal endothelial cells (CECs) during the serial passage culture needed to obtain massive quantities of cells for clinical use is a serious technical obstacle preventing the push of this regenerative therapy to clinical settings. Here, we show evidence from an animal model confirming that senescent cells are less effective in cell therapy. In addition, we propose that density-gradient centrifugation can eliminate the senescent cells and purify high potency CECs for clinical use. This simple technique might be applicable for other types of cells in the settings of regenerative medicine.
Highlights
We provide evidence to show that senescent phenotype CECs were less effective in cell-based therapy in an animal model and that non-senescent phenotype cells should be used clinically
Representative corneal endothelium images obtained by non-contact specular microscope showed that the cell density (CD) is lower in 89-year-old healthy elderly subjects than in 16-year-old healthy young subjects due to aging
We showed that corneal endothelium can be regenerated in rabbit and monkey corneal endothelial dysfunction models by injecting a cultured CEC suspension combined with a Rho-associated kinase (ROCK) inhibitor[16]
Summary
We provide evidence to show that senescent phenotype CECs were less effective in cell-based therapy in an animal model and that non-senescent phenotype cells should be used clinically. We proposed a simple procedure for purification of cultured human CECs (HCECs) by eliminating the senescent HCECs by density-gradient centrifugation. We were motivated to evaluate the effect of cell senescence on cell-based therapy and conducted experiments using a rabbit corneal endothelial dysfunction model.
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