The Limbal Epithelial Progenitors in the Limbal Niche Environment

Zhang, Yuan; Sun, Hong; Liu, Yongsong; Chen, Shuangling; Cai, Subo; Zhu, Yingting; Guo, Ping

doi:10.7150/ijms.16563

Cited by 13 publications

(9 citation statements)

References 60 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…1 ). This result resembles our success in using 2D Matrigel to isolate and expand human limbal niche progenitors 16 – 18 , 20 , 36 and suggests that the in vivo extracellular matrix components such as laminins, collagens, elastin, fibronectin, fibrillins, proteoglycans, and matricellular proteins (reviewed in ref. 37 ) collectively play an important role in the maintenance of TM phenotype.…”

Section: Discussionsupporting

confidence: 74%

Isolation and Expansion of Multipotent Progenitors from Human Trabecular Meshwork

Zhang¹,

Cai

Tseng³

et al. 2018

Sci Rep

Self Cite

View full text Add to dashboard Cite

To expand multi-potent progenitors from human trabecular meshwork (TM), we have created a new optimized method on two-dimensional (2D) followed by three–dimensional (3D) Matrigel in modified embryonic stem cell medium supplemented with 5% fetal bovine serum (MESCM + 5% FBS). The expanded TM cells were small cuboidal cells expressing TM markers such as AQP1, MGP, CHI3L1, and AnkG, embryonic stem cell (ESC) markers such as Oct4, Sox2, Nanog, and ABCG2, and neural crest (NC) markers such as p75NTR, FOXD3, Sox9, Sox10, and MSX1. Although expanded cells lost expression of these markers after passage, the cells regained the markers when Passage 2 cells were seeded on 3D Matrigel through activation of canonical BMP signaling. Such restored progenitors could differentiate into corneal endothelial cells, adipocytes, and chondrocytes but not keratocytes or osteocytes. Therefore, we have concluded that human TM harbors multipotent progenitors that can be effectively isolated and expanded using 2D Matrigel in MESCM + 5% FBS. This unique in vitro model system can be used to understand how TM is altered in glaucoma and whether such TM progenitor cells might one day be used for treating glaucoma or corneal endothelial dysfunction.

show abstract

Section: Discussionsupporting

confidence: 74%

Isolation and Expansion of Multipotent Progenitors from Human Trabecular Meshwork

Zhang¹,

Cai

Tseng³

et al. 2018

Sci Rep

Self Cite

View full text Add to dashboard Cite

show abstract

“…LSCs normally reside in the limbal palisades of Vogt. The niche of LSCs ( Figure 1 ) consists of cells, extracellular matrix, and functional mediators, such as secreted cytokines, providing a microenvironment for LSCs to play their roles, such as self-renewal [ 30 , 31 ].…”

Section: Lsc and Lsc Nichementioning

confidence: 99%

“…They divide into TACs by mitosis, retaining less stemness. Due to progressive loss of stemness along with multiple rounds of division, TACs finally divided into the terminally differentiated cells (TDCs) [ 30 ]. This process takes over two weeks [ 47 ].…”

Section: Dynamics Of Lscsmentioning

confidence: 99%

An Insight into the Difficulties in the Discovery of Specific Biomarkers of Limbal Stem Cells

Guo

Zhang

Jia

et al. 2018

IJMS

View full text Add to dashboard Cite

Keeping the integrity and transparency of the cornea is the most important issue to ensure normal vision. There are more than 10 million patients going blind due to the cornea diseases worldwide. One of the effective ways to cure corneal diseases is corneal transplantation. Currently, donations are the main source of corneas for transplantation, but immune rejection and a shortage of donor corneas are still serious problems. Graft rejection could cause transplanted cornea opacity to fail. Therefore, bioengineer-based corneas become a new source for corneal transplantation. Limbal stem cells (LSCs) are located at the basal layer in the epithelial palisades of Vogt, which serve a homeostatic function for the cornea epithelium and repair the damaged cornea. LSC-based transplantation is one of the hot topics currently. Clinical data showed that the ratio of LSCs to total candidate cells for a transplantation has a significant impact on the effectiveness of the transplantation. It indicates that it is very important to accurately identify the LSCs. To date, several putative biomarkers of LSCs have been widely reported, whereas their specificity is controversial. As reported, the identification of LSCs is based on the characteristics of stem cells, such as a nuclear-to-cytoplasm ratio (N/C) ≥ 0.7, label-retaining, and side population (SP) phenotype. Here, we review recently published data to provide an insight into the circumstances in the study of LSC biomarkers. The particularities of limbus anatomy and histochemistry, the limits of the current technology level for LSC isolation, the heterogeneity of LSCs and the influence of enzyme digestion are discussed. Practical approaches are proposed in order to overcome the difficulties in basic and applied research for LSC-specific biomarkers.

show abstract

“… 7 After cell division, one daughter cell maintains the LSC stemness while the other daughter cell becomes a transient amplifying cell (TAC), with increased proliferative potential. 8 – 11 TACs migrate out of the stem cell niche and ultimately differentiate into corneal epithelial cells. 9 LSCs are required for reconstituting the corneal epithelium after injury and also have an important role in preventing conjunctival epithelial cells from migrating onto the surface of the cornea.…”

mentioning

confidence: 99%

Hyaluronan Rich Microenvironment in the Limbal Stem Cell Niche Regulates Limbal Stem Cell Differentiation

Gesteira

Sun

Coulson-Thomas

et al. 2017

Invest. Ophthalmol. Vis. Sci.

View full text Add to dashboard Cite

PurposeLimbal epithelial stem cells (LSCs), located in the basal layer of the corneal epithelium in the corneal limbus, are vital for maintaining the corneal epithelium. LSCs have a high capacity of self-renewal with increased potential for error-free proliferation and poor differentiation. To date, limited research has focused on unveiling the composition of the limbal stem cell niche, and, more important, on the role the specific stem cell niche may have in LSC differentiation and function. Our work investigates the composition of the extracellular matrix in the LSC niche and how it regulates LSC differentiation and function.MethodsHyaluronan (HA) is naturally synthesized by hyaluronan synthases (HASs), and vertebrates have the following three types: HAS1, HAS2, and HAS3. Wild-type and HAS and TSG-6 knockout mice—HAS1−/−;HAS3−/−, HAS2Δ/ΔCorEpi, TSG-6−/−—were used to determine the importance of the HA niche in LSC differentiation and specification.ResultsOur data demonstrate that the LSC niche is composed of a HA rich extracellular matrix. HAS1−/−;HAS3−/−, HAS2Δ/ΔCorEpi, and TSG-6−/− mice have delayed wound healing and increased inflammation after injury. Interestingly, upon insult the HAS knock-out mice up-regulate HA throughout the cornea through a compensatory mechanism, and in turn this alters LSC and epithelial cell specification.ConclusionsThe LSC niche is composed of a specialized HA matrix that differs from that present in the rest of the corneal epithelium, and the disruption of this specific HA matrix within the LSC niche leads to compromised corneal epithelial regeneration. Finally, our findings suggest that HA has a major role in maintaining the LSC phenotype.

show abstract

The Limbal Epithelial Progenitors in the Limbal Niche Environment

Cited by 13 publications

References 60 publications

Isolation and Expansion of Multipotent Progenitors from Human Trabecular Meshwork

Isolation and Expansion of Multipotent Progenitors from Human Trabecular Meshwork

An Insight into the Difficulties in the Discovery of Specific Biomarkers of Limbal Stem Cells

Hyaluronan Rich Microenvironment in the Limbal Stem Cell Niche Regulates Limbal Stem Cell Differentiation

Contact Info

Product

Resources

About