First Stem Cell Therapy Recommended for Approval in European Union

The EMA, which is short for the European Medicines Agency, has recommended approval for a treatment called Holoclar.  Holoclar is the first therapy product that contains stem cells to be recommended for approval in the European Union (EU). Holoclar is being marketed as a treatment for moderate to severe limbal stem cell deficiency (LSCD) due to physical or chemical burns to the eye in adults. In fact, Holoclar is the first medicine recommended for LSCD, a condition that can result in blindness.

Holoclar can be transplanted into the eye after removal of the corneal epithelium (the outer layer of the cornea). Holoclar is made from a biopsy taken from a small, undamaged area of the patient’s cornea. These limbal stem cells are then grown in the laboratory using cell culture techniques. Holoclar is a potential alternative to transplantation for replacing altered corneal epithelium. Clnical trials with Holoclar have been shown to increase the chances of a successful corneal transplant where the injury has caused extensive eye damage. Holoclar is produced by Chiesi, a pharmaceutical company based in Parma, Italy.

The recommendation to approve Holoclar was made by the EMA’s Committee for Medicinal Products for Human Use (CHMP). CHMP made their recommendation on basis of the benefits of Holoclar, which are its ability to repair the damaged ocular surface, to improve or resolve symptoms of pain, photophobia and burning and to improve the patient’s visual acuity. This assessment was the work of the Committee for Advanced Therapies (CAT). The approved indication for Holoclar is: “Treatment of adult patients with moderate to severe limbal stem cell deficiency (defined by the presence of superficial corneal neovascularisation in at least two corneal quadrants, with central corneal involvement, and severely impaired visual acuity), unilateral or bilateral, due to physical or chemical ocular burns. A minimum of 1-2 square millimeters of undamaged limbus is required for biopsy.” CAT and CHMP considered that Holoclar provided a first treatment option for LSCD and recommended a conditional marketing authorization. The authorization is conditional because the clinical data available for Holoclar is based on studies that are ongoing as treated patients are watched after their eye surgery. This the data collection is not yet comprehensive, and additional study on the use of Holoclar needs to be conducted.

The opinion adopted by the CHMP at its December 2014 meeting is an intermediary step on Holoclar’s path to patient access. The CHMP opinion will now be sent to the European Commission for a decision on an EU-wide marketing authorization.

University of Pittsburgh Team Uses Patient’s Own Stem Cells to Clear Cloudy Corneas

The transparent portion of the center of our eyes is called the cornea. Scars on the cornea can cause an infuriating haziness across the eye. However, healing these cloudy corneas might be as simple as growing stem cells from a tiny biopsy of the patient’s undamaged eye and placing them on the injury site. This hope comes from experiments in a mouse model system conducted by researchers at the University of Pittsburgh School of Medicine. These findings were published in Science Translational Medicine and could one day rescue vision for millions of people worldwide and decrease the need for corneal transplants.

According to statistics compiled by the National Eye Institute, which is a branch of the National Institutes of Health, globally, corneal infectious diseases have compromised the vision of more than 250 million people and have blinded over 6 million of them. Additionally, trauma from burns is also a leading cause of corneal scarring.

James L. Funderburgh, Ph.D., professor of ophthalmology at Pitt and associate director of the Louis J. Fox Center for Vision Restoration of UPMC and the University of Pittsburgh, a joint program of UPMC Eye Center and the McGowan Institute for Regenerative Medicine, said, “The cornea is a living window to the world, and damage to it leads to cloudiness or haziness that makes it hard or impossible to see. The body usually responds to corneal injuries by making scar tissue. We found that delivery of stem cells initiates regeneration of healthy corneal tissue rather than scar leaving a clear, smooth surface.”

The lead author of this study, Sayan Basu, is a corneal surgeon who works at the L.V. Prasad Eye Institute in Hyderabad, India. Dr. Basu who joined with Dr. Funderburgh’s lab, has developed a technique to isolate ocular stem cells from tiny biopsies from the surface of the eye and a region between the cornea and sclera known as the limbus. Such a small biopsy heals rapidly with little discomfort and no disruption of vision. Such biopsies are banked in tissue banks and then expanded in culture, and several tests shows that even after isolation and expansion, these cells are still corneal stem cells.


“Using the patient’s own cells from the uninjured eye for this process could let us bypass rejection concerns,” Dr. Basu noted. “That could be very helpful, particularly in places that don’t have corneal tissue banks for transplant.”

Basu in collaboration with Funderburgh’s team tested these human limbal stem cells in a mouse model of corneal injury. This team used goo made of fibrin to glue the cells to the injury site. Fibrin is the protein found in blood clots, but it is also commonly used as a surgical adhesive. Application of these limbal stem cells not only induced healing of the mouse corneas, their eyes became clear again within four weeks of treatment. On the other hand, the eyes of mice that were not treated with limbal stem cells remained cloudy.


In fact, the healing was so good that Funderburgh said: “Even at the microscopic level, we couldn’t tell the difference between the tissues that were treated with stem cells and undamaged cornea. We were also excited to see that the stem cells appeared to induce healing beyond the immediate vicinity of where they were placed. That suggests the cells are producing factors that promote regeneration, not just replacing lost tissue.”

This work is the impetus behind a small pilot study presently underway in Hyderabad which will treat a handful of patients with their own corneal stem cells.

A New Way to Regrow Human Corneas

My apologies to my readers, but I was at the Free Methodist Bible Quizzing Finals at Greenville College in Illinois for the last week. I am recovering and have only the energy to write a short post for today.

The cornea is the transparent covering of the eye that transmits light from the environment to the inside of the eye, to the photoreceptor-rich retina that interprets the light information and translates them into neural signals that are sent to the visual centers of the brain.

The cornea is subject to constant wear and tear, but fortunately, a stem cell population called limbal stem cells. These stem cells constantly regenerate the cornea, and the conjunctiva, which is otherwise known as the “whites of the eye.”

Limbal stem cells


Unfortunately, the limbal stem cells can be damaged by chemicals, sparks from a welding, genetically inherited conditions, or physical trauma. Such conditions can prevent proper replacement of constantly sloughed cornea and conjunctival cells. This can seriously compromise the structural integrity and function la of the eye.

To treat patients with corneal limbal stem defects, eye surgeons have transplanted limbal cells from cadavers or used small excisions of limbal cell populations from the unaffected eye and transplanted them into the affected eye. These so-called “autologous limbal cell transplants” tend to work quite well, but there are two cuts that need to be made. Is there are way to expand limbal stem cells for clinical use? Now it appears that there is.

Scientists from the Massachusetts Eye and Ear Infirmary have used sophisticated key tracer molecules to pin down the precise cells in the eye that are capable of regeneration and repair. They then transplanted these regenerative stem cells into mice to create fully functioning corneas.

This work was published in the international journal Nature, and they predict that this method may one day help restore the sight of victims of burns and chemical injuries.

Limbal stem cells (LSC) completely renew our corneas every few weeks and repair the cornea and conjunctiva whenever they are injured. Without LSCs the cornea becomes cloudy, which severely disrupts vision. In fact, LSC deficiencies are among the commonest reasons behind blindness worldwide.

Unfortunately, the LSC population is embedded in a part of the eye where they share space with a matrix of other structures in the limbal part of the eye (FYI – the limbus is the junction between the cornea and the white of the eye).

Enter the work from the Massachusetts Eye and Ear Infirmary in Boston at the Boston Children’s Hospital, Brigham and Women’s Hospital and in collaboration with the VA Boston Healthcare System have identified a key molecule known as ABCB5, which is naturally present on the surface of LSCs.

Although ABCB5 has been known about for some time in other parts of the body, this is the first time ABCB5 has been identified on the surfaces of LSCs. Also, it is clear that ABCB5 can effectively mark LSCs.

By using molecules linked to fluorescent molecules, these scientists were able to instantly identify a pool of LSCs on donated human corneas. After transplanting these cells into the eyes of mice, they discovered that the transplanted cells were able to generate fully functioning human corneas.

Prof Markus Frank, of Boston Children’s Hospital, a lead author in the research, told the BBC: ” The main significance for human disease is we have established a molecularly defined population of cells that we can extract from donor tissue.

“And these cells have the remarkable ability to self-regenerate. We hope to drive this research forward so this can be used as a therapy.”

Harminder Dua, professor of ophthalmology at the University of Nottingham, who was not involved in this study, said: “This paper represents a very comprehensive and well conducted piece of work that takes use closer to the precise identification of stem cells.

“Applying this knowledge to a clinical setting could help improve the outcomes for patients who need corneal reconstruction.”