Human embryonic stem cells (hESCs) are an ideal seed cell sources for tissue regeneration. It is known that the culture
microenvironment is vital for the differentiation fate and the stemness preservation of hESCs. Our research establishes a
feasible and efficient strategy for inducing hESCs into limbal stem cells (LSCs)-like cells by using the conditioned media harvested
from human LSCs and the specific extracellular matrix to replicate the limbal microenvironment in vitro. These hESCs derived
LSCs-like cells (hESCs-LSCs) could highly express specific markers of LSCs and show low expression level of specific markers
of terminally differentiated corneal epithelial cells. hESCs-LSCs have strongly clonogenic and proliferative capacity and are able
to differentiate into corneal epitheloid cells in subsequential culture in vitro. These differentiated cells also display an adorable
biocompatibility with human amniotic membrane (HAM) and acelluar porcine corneal matrix (APCM) in vitro. hESCs-LSCs
give rise to stratified epithelial cell sheets on HAM and APCM and the basal cells still keep the LSCs characteristics. And in rabbit
limbal stem cell deficiency (LSCD) models, hESCs-LSCs could functionally reconstruct the damage ocular surface, satisfactorily
inhibit the invasion of corneal neovascularization, reduce inflammation reaction and partially alleviate the scar formation in
anterior corneal stroma. These findings indicate that hESCs are capable of differentiating into LSCs in vitro and the differentiated
cells may be a potential choice for ocular surface regeneration in LSCD patients.
Xinyi Wu is the correspondence author and the director of Department of Ophthalmology, Qilu Hospital of Shandong University.
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