Regenerative Medicine

A product in our regenerative medicine R & D pipeline that is intended to treat various diseases involving human epithelial components, of which limbal stem cell deficiency is a target disease for the epithelial cell sheets. A clinical trial of the epithelial cell sheets is being carried out in France, in parallel to commercialization activities.

Product Concept and Characteristics

The cornea of the human eye is composed of three main components: the epithelium, stroma, and endothelium. The corneal epithelium contains stem cells* that are responsible for metabolism. If these stem cells are depleted as a result of autoimmune diseases, burns, or other causes, the corneal epithelium on the ocular surface will no longer regenerate easily. The defective epithelial area and eventually the entire surface will be gradually covered with conjunctival and vascular tissue, leading to visual disturbance and other disorders. These disorders are collectively known as limbal stem cell deficiency, for which several therapies have proved unsuccessful. There is still no effective therapy established for this disorder.

The epithelial cell sheets for corneal regeneration are being evaluated and developed for the treatment of corneal epithelial disorders, including limbal stem cell deficiency. The epithelial cell sheet is fabricated on temperature-responsive culture surfaces from patient-derived oral mucosal epithelial cells (having similar characteristics to those of corneal epithelial cells). The cell sheet is then transplanted onto the defective part of the patient's cornea. The epithelial cell sheets for corneal regeneration has four distinct advantages:

1. There is a low likelihood of post-transplant rejection because autologous cells are used as the main starting material. (Cells harvested from individuals other than the patient are regarded as foreign and may be rejected by the patient's immune system.)
2. The transplanted sheet grafts to the damaged tissue without requiring sutures - a feature common to cell sheets used in regenerative medicine. This therapeutic approach can avoid suture-related problems arising from differing levels of surgical skill (e.g., the product is sutured in a twisted state) as well as opacification of the corneal epithelium due to suture scars. In addition, the suture-free procedure saves time and reduces the burden for both the surgeon and patient.
3. The safety risk from biological materials (e.g., infection with an unknown virus contained in biological materials) is very low, because the cell sheet does not contain bio-derived materials (e.g., amnion or blood preparations from individuals other than the patient) other than patient-derived cells (autologous cells).
4. Even patients with damaged corneal epithelium in both eyes can be treated safely, since epithelial cells from the patient's oral mucosa are used as the main starting material. (If stem cells collected from the cornea were used as the starting material, at least one of the patient's eyes must be healthy enough to tolerate the cell collection. Otherwise, it is impossible to treat either eye in such patients.)

* Stem cells :	Master cells with the potential to differentiate into a variety of cells and ability to differentiate even after undergoing cell division.