What Are Limbal Stem Cells?

The surface of the cornea is constantly renewing itself. Cells are naturally lost through everyday wear and tear, blinking and minor injuries, yet the healthy corneal surface remains remarkably stable.

A small population of cells located at the edge of the cornea plays a central role in making this possible: limbal stem cells.

A stem cell population at the border of the cornea

The cornea is the transparent tissue covering the front of the eye. Its outermost layer, the corneal epithelium, provides an important protective barrier while helping maintain the smooth and transparent surface required for vision.

At the border between the cornea and the surrounding conjunctiva lies a narrow ring of tissue called the limbus.

This is where limbal epithelial stem cells reside.

Limbal stem cells have the ability to self-renew and to generate the epithelial cells needed to continually replenish the corneal surface. In this way, a relatively small population of stem cells supports the maintenance and repair of the corneal epithelium throughout life.

Maintaining a clear corneal surface

Limbal stem cells do more than respond when the eye is injured.

During normal tissue maintenance, they generate progenitor cells that proliferate and progressively differentiate into mature corneal epithelial cells. These cells ultimately contribute to the stratified epithelium covering the cornea.

The limbal region also helps maintain the boundary between the corneal and conjunctival epithelia. When the limbal stem cell system is intact, conjunctival epithelial cells are prevented from progressively covering the transparent corneal surface.

Together, these functions make the limbus essential for maintaining a healthy, stable and transparent ocular surface.

What happens when these stem cells are damaged?

Because limbal stem cells are responsible for renewing the corneal epithelium, severe damage or loss of this population can have major consequences.

If too few functional limbal stem cells remain, the corneal surface can no longer regenerate normally. Conjunctival cells may migrate onto the cornea, blood vessels can develop in tissue that should normally remain transparent, and inflammation, scarring and corneal opacity can occur.

This condition is known as limbal stem cell deficiency (LSCD) and, when severe, can result in substantial visual impairment.

Limbal stem cells and regenerative medicine

The regenerative capacity of limbal stem cells has made them an important example of how stem cell biology can be translated into medicine.

In cell-based approaches, limbal epithelial cells can be obtained from a small amount of healthy limbal tissue and expanded outside the body to generate cells for transplantation.

This concept has already reached clinical practice. In 2015, Holoclar, an autologous treatment containing expanded human corneal epithelial cells including stem cells, became the first stem cell-based advanced therapy medicinal product to receive marketing authorization in the European Union.

This clinical precedent demonstrates something important: restoring a functional stem cell population can provide a way of rebuilding the regenerative capacity of the ocular surface.

Building on limbal stem cell biology

At Corcellys Therapeutics, limbal stem cell biology provides the scientific foundation for our lead program.

Our work builds on the regenerative potential of these cells while exploring how advances in stem cell biology, manufacturing, cryopreservation and delivery can contribute to the development of future therapies for patients with severe ocular surface disease.

Understanding the biology of limbal stem cells is therefore not only about understanding how the healthy cornea maintains itself.

It is also the starting point for understanding how we might restore that capacity when it has been lost.

Learn more

For readers interested in exploring limbal stem cells in greater depth:

Scientific article: Pellegrini G. et al. Navigating Market Authorization: The Path Holoclar Took to Become the First Stem Cell Product Approved in the European Union. Stem Cells Translational Medicine, 2018.

General overview: https://en.wikipedia.org/wiki/Limbal_stem_cell