Ex Vivo Expansion of Human Limbal Epithelial Cells Using Human Placenta-Derived and Umbilical Cord-Derived Mesenchymal Stem Cells
Authors
Sang Min Nam, Yong-Sun Maeng, Eung Kweon Kim, Kyoung Yul Seo3 and Helen Lew
Institution
Department of Ophthalmology, CHA Bundang Medical Center, CHA University, Seongnam
Country
South Korea
Year
2017
Journal
Stem Cells International - Hindawi
Abstract
Ex vivo culture of human limbal epithelial cells (LECs) is used to treat limbal stem cell (LSC) deficiency, a vision loss condition, and
suitable culture systems using feeder cells or serum without animal elements have been developed. This study evaluated the use of
human umbilical cord or placenta mesenchymal stem cells (C-MSCs or P-MSCs, resp.) as feeder cells in an animal/serum-free
coculture system with human LECs. C-/P-MSCs stimulated LEC colony formation of the stem cell markers (p63, ABCG2)
and secreted known LEC clonal growth factors (keratinocyte growth factor, β-nerve growth factor). Transforming growth
factor-β-induced protein (TGFBIp), an extracellular matrix (ECM) protein, was produced by C-/P-MSCs and resulted in an
increase in p63+ ABCG2+ LEC colonies. TGFBIp-activated integrin signaling molecules (FAK, Src, and ERK) were expressed in
LECs, and TGFBIp-induced LEC proliferation was effectively blocked by a FAK inhibitor. In conclusion, C-/P-MSCs
enhanced LEC culture by increasing growth of the LSC population by secreting growth factors and the ECM protein
TGFBIp, which is suggested to be a novel factor for promoting the growth of LECs in culture. C-/P-MSCs may be useful
for the generation of animal-free culture systems for the treatment of LSC deficiency.