Can Human Oral Mucosa Stem Cells Differentiate to Corneal Epithelia?

Sonia López,Higinio Arzate,Lía Hoz,Fátima Sofía Magaña,Beatriz Buentello,Ana Wintergerst,Eda Patricia Tenorio,Yonathan Garfias,Alejandro Navas

doi:10.3390/ijms22115976

Abstract

Human oral mucosa stem cells (hOMSCs) arise from the neural crest, they can self-renew, proliferate, and differentiate to several cell lines and could represent a good source for application in tissue engineering. Because of their anatomical location, hOMSCs are easy to isolate, have multilineage differentiation capacity and express embryonic stem cells markers such as—Sox2, Oct3/4 and Nanog. We have used SHEM (supplemented hormonal epithelial medium) media and cultured hOMSCs over human amniotic membrane and determined the cell’s capacity to differentiate to an epithelial-like phenotype and to express corneal specific epithelial markers—CK3, CK12, CK19, Pan-cadherin and E-cadherin. Our results showed that hOMSCs possess the capacity to attach to the amniotic membrane and express CK3, CK19, Pan-Cadherin and E-Cadherin without induction with SHEM media and expressed CK12 or changed the expression pattern of E-Cadherin to a punctual-like feature when treated with SHEM media. The results observed in this study show that hOMSCs possess the potential to differentiate toward epithelial cells. In conclusion, our results revealed that hOMSCs readily express markers for corneal determination and could provide the ophthalmology field with a therapeutic alternative for tissue engineering to achieve corneal replacement when compared with other techniques. Nevertheless, further studies are needed to develop a predictable therapeutic alternative for cornea replacement.

Highlights

Stem cells have three main characteristics—they can self-renew, proliferate and differentiate to several cell phenotypes [1]
Human oral mucosa stem cells are adult stem cells originating from the neural crest [26]
The differences in expression the levels can be used to track the capacity to differentiate into specific phenotypes [27,28,29,30]; in the case of eyes, cells positive to Sox2 and Pax6 might have a better chance of acquiring a corneal phenotype [31]

Summary

Introduction

Stem cells have three main characteristics—they can self-renew, proliferate and differentiate to several cell phenotypes [1]. The oral cavity is easy to access and stem cells can be isolated from several sites such as—bone marrow, dental pulp of permanent and deciduous teeth, dental follicle, dental germ, apical papilla, oral mucosa, periosteum, periodontal ligament, salivary glands, and adipose tissues [5,6] Of these sites, the oral mucosa is privileged since it can regenerate quickly and ages slowly in comparison to other tissues in the body. A special population of stem cells from the lamina propria of the human oral mucosa (hOMSCs) is isolated and possesses great potential for differentiation These cells express embryonic stem cell (ESC) markers; Tra, Tra, SSEA4, Oct, Sox and Nanog, and the NC marker; nestin, besides the canonical MSC markers CD73, CD90, CD105 [8]. These cells have been found to differentiate into NC lineages such as—astrocytes, dopaminergic neurons, cardiomyocytes, and osteoblasts [8,9,10,11,12,13]

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Results

Conclusion