Mesenchymal Stem Cells Treat Dry Eye Syndrome in Mice

Nearly 10% of all Americans suffer from Dry eye syndrome (DES), which makes this disorder one of the most common ocular diseases. Most of the currently-available treatments are palliative, but few therapeutic agents target the biological causes of DES. Many factors contribute to DES, but one of the most important factors in the cause of DES is inflammation of the ocular surface.

Since mesenchymal stem cells (MSCs) have been shown to suppress inflammation, using MSCs to treat DES seems to be a viable treatment option. MSCs can also repair tissues by regulating excessive immune responses in various diseases.

Thus Joo Youn Oh from the Seoul National University in Seoul, Korea and his colleagues investigated the therapeutic potential of MSCs in a mouse model of an inflammation-mediated dry eye. They induced DES in these mice by injecting a plant protein into the eye that grabs sugars into the eye. This protein injection dries out the eyes in these mice and induces a kind of DES-like condition.

Then they found that the administration of MSCs into the eye reduced the infiltration of immune cells into the eye and overall decreased eye inflammation. Administration of MSCs into the eye also significantly increased tear production and also increased the number of conjunctival goblet cells, which secrete lubricating mucus so that the eye lid slides gently over the eye surface. Further investigation showed that the structural integrity of the eye surface, known as the cornea, was well-preserved by MSCs.

When taken together, ocular administration of MSCs seem to suppress the inflammation that either accompanies or contributes to DES.  These results also suggest that MSCs may provide a potential therapy for those diseases that cause inflammation of the ocular surface and adversely affect the eye because of it.  

New Approach for Corneal Stem Cell Treatments

More than 8 million people worldwide suffer from corneal blindness; a form of blindness that results from cloudiness of the outermost covering of the eye, the cornea.

Usually, the cornea copes quite well with minor injuries or scrapes and scratches. If the cornea is scratched, healthy cells slide over quickly and patch the injury before infection occurs and vision is not adversely affected. However, if the scratch penetrates the cornea more deeply, then the healing process takes longer and can result in greater pain, blurred vision, tearing, redness, and extreme sensitivity to light. Such scratches may require professional treatment. Even deeper scratches can also cause corneal scarring, which results in a haze on the cornea that can greatly impair vision, and the patient might require a corneal transplant.

Alternatively, corneal stem cells can help heal a damaged cornea; especially in those cases where the cornea has been damaged to the point where the native stem cell population has suffered irreparable damage (e.g., chemical burns, eye infections, or cases where the patient was born with a corneal stem cell deficiency).

A feasible treatment for such cases is a corneal stem cell transplant from another eye or from cultured corneal stem cells. Unfortunately, this procedure has not yet been standardized to date.

Fortunately, researchers at the Eye Program at the Cedar-Sinai Regenerative Medicine Institute have designed a fast, new procedure for preparing human amniotic membrane to use as a scaffold for corneal stem cells. The membrane provides a foundation that supports the growth of stem cells that can be grafted onto the cornea.

To date, a standardized method does not exist for the preparation of amniotic membranes for culturing corneal stem cells. Many methods use chemicals and may leave behind amniotic cells and membrane components.

This new procedure, however, takes less than one minute and ensures complete amniotic cell removal and preservation of amniotic membrane components, and, as an added bonus, supports the overall growth of various stem and tissue cells.

“We believe that this straightforward and relatively fast procedure would allow easier standardization of amniotic membrane as a valuable stem cell support and improve the current standard of care in corneal stem cell transplantation,” said the lead author of this work Alexander Ljubimov, the director of the Eye Program at the Cedar-Sinai Regenerative Medicine Institute. “This new method may provide a better method for researchers, transplant corneal surgeons, and manufacturing companies alike.”

The amniotic membrane has several beneficial properties for corneal stem cells culturing and use in corneal transplantations. For this reason it is an attractive framework for the growth and culture of corneal stem cells and for corneal transplantations.

The new method for amniotic membrane preparation will provide a fast way to create scaffolds for cell expansion and might potentially streamline clinical applications of cell therapies.

A New Technique to Fix Damaged Eyes With Stem Cells

Engineers at the University of Sheffield have invented a new delivery technique for delivering stem cells to eyes. They have high hopes that this technique will help repair the eyes of those patients who have suffered damage to their eyes.

The front of the eye is bordered by the transparent cornea, which transmits light to the lens. The cornea is exposed to the outside world and if there is an accident that affects the eye, the cornea is usually the part that takes a beating. The cornea undergoes constant turnover as dead cells are constantly sloughed from the cornea during blinking. At the junction between the cornea and the sclera is an area called the limbus. Located at the limbus is a population of limbal epithelial stem cells or LESCs. LESCs have many features commonly observed in other stem cells, such as small size, high nuclear to cytoplasmic ratio, and they lack expression of molecules commonly found in mature corneal cells, such as cytokeratins 3 and 12.

Human Limbus

LESCs are slow-growing, but in the event of injury they can become highly proliferative (See Lavker R.M, Sun T.T. Epithelial stem cells: the eye provides a vision. Eye. 2003;17:937–942. DOI: 10.1038/sj.eye.6700575).

LESC deficiency can result from chemical or thermal burns to the eye or as a result of certain inherited diseases. Partial or full LESC deficiency causes abnormal corneal wound healing and surface integrity. Also LESC deficiency causes the conjunctiva to grow over the cornea, and this is disastrous for the eye because the cornea is devoid of blood vessels, which is the reason why it is transparent. However the conjunctiva (the white of the eye) is filled with blood vessels and is not transparent. Thus chronic inflammation, recurrent erosion, ulceration and stromal scarring can occur and cause painful vision loss

Long term restoration of visual function requires renewal of the corneal epithelium, and this requires the placement of a new stem cell population by means of a limbus graft. From where do you get a new limbus for transplantation? Autografts use limbal cells from the good eye, but this runs the risk of scarring the cornea of the other eye.procedure is the use limbal cells from cadavers (limbal allografts). Also, making sure that the graft adheres to the requires the use of sutures, but these sutures can cause substantial amounts of irritation. Therefore, the Sheffield research group designed a new technique.

With this new technique, a disk made of biodegradable material is loaded with limbal stem cells and then placed over the eye. This disc has an outer ring pockmarked with small niches for stem cells can hide. The material in the center of the disc is thinner than that on the edges, and therefore, the center of the disc biodegrades faster. This releases the stem cells in center of the disc into the cornea where they can grow and help repair it.

Because these small niches in the disc resemble the stem cells niches found in the limbus, these discs do an excellent job of nurturing the limbal stem cells and distributing them to the cornea. Limbal grafts are either done with amniotic membrane as a carrier, but this procedure leads to increased inflammation in the eye and there is a chance that the grafts will not integrate into the limbus. The biodegradable disc groups the limbal stem cells into clusters that are more likely to ingrate into the limbus.

According to Professor Sheila MacNeil, “Laboratory tests have shown that the membranes will support cell growth, so the next stage is to trial this in patients in India, working with our colleagues in the LV Prasad Eye Institute in Hyderabad. One advantage of our design is that we have made the disc from materials already in use as biodegradable sutures in the eye so we know they won’t cause a problem in the body. This means that, subject to the necessary safety studies and approval from Indian Regulatory Authorities, we should be able to move to early stage clinical trials fairly quickly.”

In the developing world, corneal blindness is rather common in some professions and treating it is a rather pressing problem. High instances of chemical burns to the eye or accidental damage to the eye are common, but complex treatment strategies such as amniotic membrane grafts are not available to the general public.

This technique also possibilities in more developed countries, since current techniques use donor tissue to deliver the cultured cells, and this requires a tissue bank to which some people do not have access. Also, the use of the cell-impregnated disk will reduce the risk of disease transmission with grafts.