Lysophosphatidic acid improves corneal endothelial density in tissue culture by stimulating stromal secretion of interleukin‐1β

• Published in: Journal of cellular and molecular medicine 2020-06, Vol.24 (12), p.6596-6608
• Main Authors: Hsueh, Yi‐Jen, Meir, Yaa‐Jyuhn James, Lai, Jui‐Yang, Chen, Hung‐Chi, Ma, David Hui‐Kang, Huang, Chieh‐Cheng, Lu, Tsai‐Te, Cheng, Chao‐Min, Wu, Wei‐Chi
• Format: Article
• Language: English
• Subjects: Animals; Antibodies; Cell Count; Cell culture; Cell cycle; Cell density; Cell growth; Cell proliferation; Cell Proliferation - drug effects; Cloning; Cornea; corneal endothelial cell (CEC); Corneal transplantation; Cytokines; Endothelial cells; Endothelial Cells - metabolism; Endothelium; Endothelium, Corneal - drug effects; Fibroblasts; Growth factors; Humans; Interleukin-1beta - metabolism; Interleukin‐1β (IL‐1β); Kinases; Lysophosphatidic acid; lysophosphatidic acid (LPA); Lysophospholipids - pharmacology; Mesenchyme; Organ Culture Techniques; Original; Proteins; Rabbits; Stromal cells; Stromal Cells - drug effects; Stromal Cells - metabolism; stromal‐endothelial interactions; Tissue culture; Wound Healing
• ISSN: 1582-1838; 1582-4934
• DOI: 10.1111/jcmm.15307

The short supply of donor corneas is exacerbated by the unsuitability of donors with insufficient endothelial cell density. Few studies have investigated promoting corneal endothelial cell proliferation to increase the endothelial cell density. We hypothesize that pre‐transplantation treatment of proliferative tissue‐cultivated corneas may increase corneal endothelial cell density. We observed that the airlift cultures were superior to immersion cultures with respect to both transparency and thickness. In this tissue culture system, we observed that lysophosphatidic acid increased the rabbit corneal endothelial cell density, number of BrdU‐positive cells and improve wound healing. We also observed an indirect effect of lysophosphatidic acid on corneal endothelial cell proliferation mediated by the stimulation of interleukin‐1β secretion from stromal cells. Human corneal tissues treated with lysophosphatidic acid or interleukin‐1β contained significantly more Ki‐67‐positive cells than untreated group. The lysophosphatidic acid‐ or interleukin‐1β‐treated cultured tissue remained hexagon‐shaped, with ZO‐1 expression and no evidence of the endothelial‐mesenchymal transition. Our novel protocol of tissue culture may be applicable for eye banks to optimize corneal grafting.