scholarly journals Differentiation Induction of Human Stem Cells for Corneal Epithelial Regeneration

2020 ◽  
Vol 21 (21) ◽  
pp. 7834
Author(s):  
Kasem Theerakittayakorn ◽  
Hong Thi Nguyen ◽  
Jidapa Musika ◽  
Hataiwan Kunkanjanawan ◽  
Sumeth Imsoonthornruksa ◽  
...  

Deficiency of corneal epithelium causes vision impairment or blindness in severe cases. Transplantation of corneal epithelial cells is an effective treatment but the availability of the tissue source for those cells is inadequate. Stem cells can be induced to differentiate to corneal epithelial cells and used in the treatment. Multipotent stem cells (mesenchymal stem cells) and pluripotent stem cells (embryonic stem cells and induced pluripotent stem cells) are promising cells to address the problem. Various protocols have been developed to induce differentiation of the stem cells into corneal epithelial cells. The feasibility and efficacy of both human stem cells and animal stem cells have been investigated for corneal epithelium regeneration. However, some physiological aspects of animal stem cells are different from those of human stem cells, the protocols suited for animal stem cells might not be suitable for human stem cells. Therefore, in this review, only the investigations of corneal epithelial differentiation of human stem cells are taken into account. The available protocols for inducing the differentiation of human stem cells into corneal epithelial cells are gathered and compared. Also, the pathways involving in the differentiation are provided to elucidate the relevant mechanisms.

Author(s):  
Edward J. Holland ◽  
Mayank Gupta

The corneal epithelium is a rapidly regenerating, stratified squamous epithelium. Homeostasis of corneal epithelial cells is an important prerequisite, not only for the integrity of the ocular surface, but also for the visual function. The maintenance of a healthy corneal epithelium under both normal and wound-healing conditions is achieved by a population of stem cells located in the basal layer of limbal epithelium. The Limbus represents the transition zone between the peripheral cornea and the bulbar conjunctiva. The stem cells from the limbus generate the transient amplifying cells that migrate, proliferate, and differentiate to replace lost or damaged corneal epithelial cells. In patients with aniridia, there is a primary dysfunction of these limbal stem cells (see Figure 6.1). The cornea is affected clinically in 90 percent of the patients with aniridia. In most cases, the cornea in aniridic patients appears normal and transparent during infancy and childhood. However, during the early teens, the cornea begins to show changes. The early changes are marked by the in-growth of opaque epithelium from the limbal region into the peripheral cornea, which represents conjunctival epithelial cells, goblet cells, and blood vessels in the corneal epithelium. These changes gradually progress toward the central cornea and may cause corneal epithelial erosions and epithelial abnormalities that eventually culminate in opacification of the corneal stroma, which leads to vision loss. With the gradual loss of limbal stem cells, the entire cornea becomes covered with conjunctival cells. Eventually, many patients develop total limbal stem cell deficiency. These abnormalities usually become more pronounced with aging. The corneal abnormalities seen in aniridia are collectively termed “aniridic keratopathy”. Significant corneal opacification may occasionally be the initial manifestation of aniridia. Abnormal tear film stability and meibomian gland dysfunction are also observed in patients with aniridia. This can lead to dry eyes, aggravating corneal erosion and ulceration observed in aniridic patients. Sometimes, aniridia is associated with “Peter’s anomaly,” in which central corneal opacity is present at birth along with defects in the corneal endothelium and Descemet’s membrane.


2014 ◽  
Vol 998-999 ◽  
pp. 312-315
Author(s):  
Fan Wang ◽  
Bo Ren ◽  
Yi Ning Yan

Purpose: The adult corneal epithelium is maintained by a population of limbal stem cells (LSCs), transmembrane protein prominin, regarded as stem cell marker was investigated on mouse corneal tissue, to study weather contains CD133-expressing cells and their distribution. Methods: Enucleated mouse eyes were embedded in OCT and cryosections were performed for mmunohistochemical studies using the avidin-biotin-peroxidase complex (ABC) procedure. Meanwhile, dissected mouse corneas were analyzed by westernblot. Results: In the adult mouse, 13A4 immunoreactivity was detected at the apical side of superficial corneal epithelium, including the limbus region, but not by stroma and endothelium. 115 KDa protein was approved in corneal tissue by Westernblot. Conclusions: The stem cell activity does not occur along the limbus but presumably presented by small portion of corneal epithelial cells which may hold a similar properties of stem cells.


2018 ◽  
Vol 8 (1) ◽  
Author(s):  
Ryuhei Hayashi ◽  
Yuki Ishikawa ◽  
Tomohiko Katayama ◽  
Andrew J. Quantock ◽  
Kohji Nishida

2020 ◽  
Vol 15 (3) ◽  
pp. 1409-1426 ◽  
Author(s):  
Núria Nieto-Nicolau ◽  
Beatriz Martín-Antonio ◽  
Claudia Müller-Sánchez ◽  
Ricardo P Casaroli-Marano

Aim: To determine the potential of mesenchymal stem cells (MSC) for corneal epithelial regeneration in vitro. Materials & methods: Bone marrow MSC (BM-MSC) and adipose tissue MSC were analyzed for corneal epithelial and mesenchymal markers, using limbal stem cells and corneal cells as controls. MSC with better potential were cultured with specific mediums for epithelial induction. Transepithelial electric resistance and wound healing assay with human corneal epithelial cells were performed. Results: BM-MSC showed better potential, increased corneal markers, and higher transepithelial electric resistance values when induced with limbal epithelial culture medium. Induced BM-MSC promoted better wound healing of human corneal epithelial cells by paracrine secretion. Conclusion: BM-MSC has potential for corneal epithelial induction in a protocol compatible with human application.


2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Yijian Li ◽  
Lingling Ge ◽  
Xia Chen ◽  
Yumei Mao ◽  
Xianliang Gu ◽  
...  

AbstractRegeneration/repair after injury can be endowed by adult stem cells (ASCs) or lineage restricted and even terminally differentiated cells. In corneal epithelium, regeneration after a large wound depends on ASCs (limbal epithelial stem cells, LESCs), whereas repair after a small wound is LESCs-independent. Here, using rat corneal epithelial wounds with different sizes, we show that YAP activation promotes the activation and expansion of LESCs after a large wound, as well as the reprogramming of local epithelial cells (repairing epithelial cells) after a small wound, which contributes to LESCs-dependent and -independent wound healing, respectively. Mechanically, we highlight that the reciprocal regulation of YAP activity and the assembly of cell junction and cortical F-actin cytoskeleton accelerates corneal epithelial healing with different-sized wounds. Together, the common YAP activation and the underlying regulatory mechanism are harnessed by LESCs and lineage-restricted epithelial cells to cope with corneal epithelial wounds with different sizes.


2010 ◽  
Vol 80 ◽  
pp. S44-S45
Author(s):  
S. Yoshida ◽  
M. Yasuda ◽  
M. Miyashita ◽  
Y. Tetsu ◽  
K. Tsubota ◽  
...  

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