Abstract
Corneal injury is a commonly encountered clinical problem which led to vision loss and impairment that affects millions of people worldwide. Currently, the available treatment in clinical practice is corneal transplantation, which is limited by the accessibility of donors. Corneal tissue engineering appears to be a promising alternative for corneal repair. However, current experimental strategies of corneal tissue engineering are insufficient due to inadequate differentiation of stem cell into keratocytes and thus cannot be applied in clinical practice. In this review, we aim to clarify the role and effectiveness of both biochemical factors, physical regulation, and the combination of both to induce stem cells to differentiate into keratocytes. We will also propose novel perspectives of differentiation strategy that may help to improve the efficiency of corneal tissue engineering.
Highlights
The pathophysiology of corneal scar formation is still poorly understood, the current lack of treatment to restore the structure of the collagen fibrils and regain vision
The induction of keratocyte differentiation by keratocyte differentiation media (KDM) has been confirmed in various kinds of stem cells, including adipose-derived mesenchymal-derived stem cells (MSCs) (ASCs) [1], bone marrow-derived MSCs (BMSCs) [36], corneal stromal stem cells (CSSCs), [30], induced pluripotent stem cells [33, 60], and periodontal ligament stem cells (PDLSCs) [42]
Chan et al cocultured human embryonic stem cells (ESCs) with PA6 to gain neural crest lineage cells (NCCs) before culturing the NCCs in the pellet model with KDM, which resulted in upregulated gene expression of keratocyte-specific markers, as well as the cells exhibiting a keratocytelike dendritic morphology suggesting that the cells deriving from human ESCs were more sufficient as compared to induced pluripotent stem cells (iPSC) [32]
Summary
The cornea is the outermost structure—a highly organized and specialized transparent tissue that plays a vital role in both the refraction of light onto the retina and protecting the eye from infectious agents. When the cornea is injured, activated keratocytes in the corneal stroma will transform into fibroblasts and myofibroblasts and subsequently migrate to the wound for tissue remodeling, including alignment of collagen fibrils. Under pathophysiological conditions, a fibrotic process may occur, resulting in corneal scar formation, including misaligned collagen fibrils. The pathophysiology of corneal scar formation is still poorly understood, the current lack of treatment to restore the structure of the collagen fibrils and regain vision. The research has mainly focused on attempts to create artificial corneal constructs to implant clinically in patients, which could potentially solve the problem of limited donors. In these attempts, stem cells are commonly used and differentiated into corneal keratocytes. We will propose novel perspectives of differentiation strategy that may help to improve the efficiency of corneal tissue engineering
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