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Published August 2013 | Published
Journal Article Open

Human Fetal Keratocytes Have Multipotent Characteristics in the Developing Avian Embryo

Abstract

The human cornea contains stem cells that can be induced to express markers consistent with multipotency in cell culture; however, there have been no studies demonstrating that human corneal keratocytes are multipotent. The objective of this study is to examine the potential of human fetal keratocytes (HFKs) to differentiate into neural crest-derived tissues when challenged in an embryonic environment. HFKs were injected bilaterally into the cranial mesenchyme adjacent to the neural tube and the periocular mesenchyme in chick embryos at embryonic days 1.5 and 3, respectively. The injected keratocytes were detected by immunofluorescence using the human cell-specific marker, HuNu. HuNu-positive keratocytes injected along the neural crest pathway were localized adjacent to HNK-1-positive migratory host neural crest cells and in the cardiac cushion mesenchyme. The HuNu-positive cells transformed into neural crest derivatives such as smooth muscle in cranial blood vessels, stromal keratocytes, and corneal endothelium. However, they failed to form neurons despite their presence in the condensing trigeminal ganglion. These results show that HFKs retain the ability to differentiate into some neural crest-derived tissues. Their ability to respond to embryonic cues and generate corneal endothelium and stromal keratocytes provides a basis for understanding the feasibility of creating specialized cells for possible use in regenerative medicine.

Additional Information

© 2013 Mary Ann Liebert, Inc. Received for publication January 5, 2013; Accepted after revision March 4, 2013; Prepublished on Liebert Instant Online March 6, 2013. This work was supported by the National Eye Institute EY022158 (P.Y.L.), the National Institute of Health DE16459 (M.E.B.), the National Eye Institute K08EY019714 ( J.R.C.), and grants from Fight for Sight, the Knights Templar Eye Foundation, and an Unrestricted Grant from Research to Prevent Blindness ( J.R.C.). A portion of this work was previously presented in two abstracts: 1. JR Chao, M Bronner-Fraser, and PY Lwigale. Stem-cell properties of human corneal keratocytes. ARVO Meeting Abstracts, April 11, 2009, 50:2049. 2. JR Chao, M Bronner-Fraser, and PY Lwigale. Corneal plasticity: characterization of the multipotentiality of human keratocytes. ARVO Meeting Abstracts, April 11, 2008, 49:4812.

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August 19, 2023
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