Chunyi Shao1, Yao Fu, Wenjuan Lu, Xianqun Fan. 1. Department of Ophthalmology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Abstract
BACKGROUND: The global shortage of donor corneas has motivated the development of bioengineered corneas. Although corneal endothelium has been reconstituted using corneal endothelial cells (CEC) and precursor cells with various carrier materials, all of the current options require corneal tissue and are also limited by the scarcity of donor corneas. Here, we explored the feasibility of inducing bone marrow-derived endothelial progenitor cells (BEPC) to differentiate into CEC for the repair of corneal endothelial defects. MATERIALS AND METHODS: BEPC were isolated from human fetal bone marrow, and identified using several antigen markers. BEPC were cocultured with CEC for 10 days in a transwell system with conditioned medium from CEC, and cell transdifferentiation was then examined. With a porcine corneal acellular matrix (PCACM) as the carrier, the induced BEPC were transplanted onto a cat's cornea from which Descemet's membrane and the endothelium had been stripped. RESULTS: The induced BEPC resembled CEC in polygonal shape, expressing aquaporin-1, tightly opposed cell junctions, and neurone-specific enolase. Twenty-eight days after surgery, the transparency gradually returned to the corneas transplanted with the induced BEPC on PCACM. CONCLUSIONS: Human fetal BEPC transdifferentiate into corneal endothelial-like cells in vitro. Features of the induced BEPC indicated that they may be useful for the repair of corneal endothelial dysfunction.
BACKGROUND: The global shortage of donor corneas has motivated the development of bioengineered corneas. Although corneal endothelium has been reconstituted using corneal endothelial cells (CEC) and precursor cells with various carrier materials, all of the current options require corneal tissue and are also limited by the scarcity of donor corneas. Here, we explored the feasibility of inducing bone marrow-derived endothelial progenitor cells (BEPC) to differentiate into CEC for the repair of corneal endothelial defects. MATERIALS AND METHODS: BEPC were isolated from human fetal bone marrow, and identified using several antigen markers. BEPC were cocultured with CEC for 10 days in a transwell system with conditioned medium from CEC, and cell transdifferentiation was then examined. With a porcine corneal acellular matrix (PCACM) as the carrier, the induced BEPC were transplanted onto a cat's cornea from which Descemet's membrane and the endothelium had been stripped. RESULTS: The induced BEPC resembled CEC in polygonal shape, expressing aquaporin-1, tightly opposed cell junctions, and neurone-specific enolase. Twenty-eight days after surgery, the transparency gradually returned to the corneas transplanted with the induced BEPC on PCACM. CONCLUSIONS:Human fetal BEPC transdifferentiate into corneal endothelial-like cells in vitro. Features of the induced BEPC indicated that they may be useful for the repair of corneal endothelial dysfunction.
Authors: Yinyin Chen; Kevin Huang; Martin N Nakatsu; Zhigang Xue; Sophie X Deng; Guoping Fan Journal: Hum Mol Genet Date: 2012-12-20 Impact factor: 6.150