Limbal Epithelial and Mesenchymal Stem Cell Therapy for Corneal Regeneration

Abstract

Corneal pathologies are a major cause of blindness and visual impairment, especially in the developing world. However, not only is there a global shortage of donor corneal tissue, but a significant proportion of these blinding pathologies also carry an unfavourable long-term prognosis for conventional corneal transplantation. In the last few decades, there has been a spurt of research on developing alternate approaches to address corneal blindness, including stem cell therapy. After the discovery of epithelial stem cells at the limbus, successful cell-based approaches to treat severe ocular surface disease were developed and have subsequently become widely practised across the world. More recently, mesenchymal stem cells were identified near the epithelial stem cells at the limbus, providing a unique opportunity to develop regenerative therapies for both corneal epithelial and stromal pathologies. This review firstly emphasises on qualifying limbal stem cells as either epithelial or mesenchymal and then summarises all the existing knowledge on both cell types and their individual roles in corneal regeneration. The review describes the history, indications, techniques, and outcomes of the different methods of limbal epithelial stem cell transplantation and elaborates on the potential applications of limbal mesenchymal stem cell therapy. ARTICLE HISTORY

Derivation and Characterization of EGFP-Labeled Rabbit Limbal Mesenchymal Stem Cells and Their Potential for Research in Regenerative Ophthalmology

“…They are thought to provide sufficient conditions for the normal functioning of LESCs [ 11 , 12 ]. These cells are used in the development of approaches for treating not only corneal stroma pathologies, such as scars, ulcers, and burns but also epithelium loss [ 13 ].…”

Regenerative Approaches and Future Trends for the Treatment of Corneal Burn Injuries

“…Another population of cells with MSC characteristics (LMSCs) exists in the corneal stroma and limbus [22]. These cells localize sub-adjacent to the limbal basement membrane and were found to enhance the viability as well as potency of the LESCs [2]. Importantly, LMSCs show multipotent features comprising differentiation into keratocytes, and perform essential corneal duties such as production of normal corneal extracellular matrix components including collagens.…”

“…Morbidity from corneal injuries ranges from mild to potentially life threatening, hence impinging negatively on the quality of life and heavily on health care systems. The corneal epithelial cells have very high turnover (every 4 to 7 days) and allow the corneal surface to regenerate continuously [2]. The limbus, where the adult (epithelial and mesenchymal) stem cells reside, is the main source of corneal epithelial cells.…”

“…Med. 2021, 10, x FOR PEER REVIEW 2 of 16 cells have very high turnover (every 4 to 7 days) and allow the corneal surface to regenerate continuously [2]. The limbus, where the adult (epithelial and mesenchymal) stem cells reside, is the main source of corneal epithelial cells.…”

Bioengineered Corneas Entering the Clinical Realm

“…Stem cell replacement within the stroma by direct infusion of mesenchymal stromal cells is now entering preclinical and early clinical trials with promising results (Basu et al 2014;Shukla et al 2019). Most recently, extracellular vesicles from the mesenchymal stromal cells have been shown to restore clarity to hazy corneas by reducing the fibrosis in mouse corneas (Shojaati et al 2019).…”