Signaling Pathways Impact on Induction of Corneal Epithelial-like Cells Derived from Human Wharton’s Jelly Mesenchymal Stem Cells
Issued Date
2022-03-01
Resource Type
ISSN
16616596
eISSN
14220067
Scopus ID
2-s2.0-85126090509
Pubmed ID
35328499
Journal Title
International Journal of Molecular Sciences
Volume
23
Issue
6
Rights Holder(s)
SCOPUS
Bibliographic Citation
International Journal of Molecular Sciences Vol.23 No.6 (2022)
Suggested Citation
Nguyen H.T., Theerakittayakorn K., Somredngan S., Ngernsoungnern A., Ngernsoungnern P., Sritangos P., Ketudat-Cairns M., Imsoonthornruksa S., Assawachananont J., Keeratibharat N., Wongsan R., Rungsiwiwut R., Laowtammathron C., Bui N.X., Parnpai R. Signaling Pathways Impact on Induction of Corneal Epithelial-like Cells Derived from Human Wharton’s Jelly Mesenchymal Stem Cells. International Journal of Molecular Sciences Vol.23 No.6 (2022). doi:10.3390/ijms23063078 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/83803
Title
Signaling Pathways Impact on Induction of Corneal Epithelial-like Cells Derived from Human Wharton’s Jelly Mesenchymal Stem Cells
Other Contributor(s)
Abstract
Corneal epithelium, the outmost layer of the cornea, comprises corneal epithelial cells (CECs) that are continuously renewed by limbal epithelial stem cells (LESCs). Loss or dysfunction of LESCs causes limbal stem cell deficiency (LSCD) which results in corneal epithelial integrity loss and visual impairment. To regenerate the ocular surface, transplantation of stem cell-derived CECs is necessary. Human Wharton’s jelly derived mesenchymal stem cells (WJ-MSCs) are a good candidate for cellular therapies in allogeneic transplantation. This study aimed to test the effects of treatments on three signaling pathways involved in CEC differentiation as well as examine the optimal protocol for inducing corneal epithelial differentiation of human WJ-MSCs. All-trans retinoic acid (RA, 5 or 10 µM) inhibited the Wnt signaling pathway via suppressing the translocation of β-catenin from the cytoplasm into the nucleus. SB505124 downregulated the TGF-β signaling pathway via reducing phosphorylation of Smad2. BMP4 did not increase phosphorylation of Smad1/5/8 that is involved in BMP signaling. The combination of RA, SB505124, BMP4, and EGF for the first 3 days of differentiation followed by supplementing hormonal epidermal medium for an additional 6 days could generate corneal epithelial-like cells that expressed a CEC specific marker CK12. This study reveals that WJ-MSCs have the potential to transdifferentiate into CECs which would be beneficial for further applications in LSCD treatment therapy.