Successful Clinical Implementation of Corneal Epithelial Stem Cell Therapy for Treatment of Unilateral Limbal Stem Cell Deficiency

Abstract

The corneal epithelium is maintained by a population of stem cells known as limbal stem cells (LSCs) due to their location in the basal layer of the outer border of the cornea known as the limbus. Treatment of limbal stem cell deficiency (LSCD) has been achieved with transplantation of ex vivo expanded LSCs taken from a small biopsy of limbus. This is a relatively new technique, and as such, specific national or international guidance has yet to be established. Because of the lack of such specific guidance, our group has sought to minimize any risk to the patient by adopting certain modifications to the research methodologies in use at present. These include the replacement of all non‐human animal products from the culture system and the production of all reagents and cultures under Good Manufacturing Practice conditions. In addition, for the first time, a strictly defined uniform group of patients with total unilateral LSCD and no other significant ocular conditions has been used to allow the success or failure of treating LSCD to be attributable directly to the proposed stem cell therapy. A prospectively designed study with strict inclusion and exclusion criteria was used to enroll patients from our database of patients with unilateral LSCD. Eight eyes of eight consecutive patients with unilateral total LSCD treated with ex vivo expanded autologous LSC transplant on human amniotic membrane (HAM) with a mean follow‐up of 19 (RANGE) months were included in the study. Postoperatively, satisfactory ocular surface reconstruction with a stable corneal epithelium was obtained in all eyes (100%). At last examination, best corrected visual acuity improved in five eyes and remained unchanged in three eyes. Vision impairment and pain scores improved in all patients (p < .05). This study demonstrates that transplantation of autologous limbal epithelial stem cells cultured on HAM without the use of non‐human animal cells or products is a safe and effective method of reconstructing the corneal surface and restoring useful vision in patients with unilateral total LSCD. STEM CELLS 2010;28:597–610

Mesenchymal Stem Cells: Possibilities of New Treatment Options

“…With aniridia, due to a mutation in PAX6 , it is thought that the niche for limbal stem cells is affected, which results in limbal stem cell dysfunction and dysregulation (Ramaesh et al 2003(Ramaesh et al , 2005 . Acquired causes include chemical and thermal burns to the surface of the eye that result in direct damage and loss to the limbal stem cells and probably also alteration of their niche (Kolli et al 2010 ) . Contact lens wear can also result in limbal stem cell defi ciency, either as a result of chemical damage from the solutions used, mechanical damage to the corneal and limbal surfaces, or a combination of these two processes.…”

“…With limbal stem cell defi ciency this is not possible, and the normal corneal epithelium on the corneal transplant is not renewed, causing the transplant to fail. Corneal transplantation is, however, a viable option in limbal stem cell defi ciency to treat any stromal or endothelial damage present only as a second procedure once the limbal stem cell defi ciency has been rectifi ed (Kolli et al 2010 ) .…”

“…Conventional surgical management of limbal stem cell defi ciency involves transplantation of limbal tissue grafts (Kolli et al 2010 ;Kenyon and Rapoza 1995 ;Kenyon and Tseng 1989 ) . They can be autologous if the patient's other eye is healthy or allogeneic from living or cadaveric donors.…”

Editorial: Our Top 10 Developments in Stem Cell Biology over the Last 30 Years

“…If the damage is unilateral, it is possible to excise a small amount of tissue from the limbus of the healthy eye and after appropriate culture, colonies enriched in limbal stem cells can be derived. Attachment of these cells to small pieces of human amniotic membrane or culture of single cell suspension on mitotically inactivated feeder cells allows them to be engrafted into the surgically exposed limbus of the damaged eye whereupon the stem cells can recolonize their intended niche [62,63] eventually restoring sight. The technique also avoids the need for drugs to suppress immunity and means there is no chance of the implanted cells being rejected.…”

Limbal Stem Cell Transplantation and Corneal Neovascularization

“…Since then, transplantation of cultivated epithelial (stem) cells has become a treatment of choice for numerous LSCD patients worldwide. While the outcomes are promising, the variability of methodologies used to expand the cells, points to an underlying need for better standardization of ex vivo cultivation-based therapies and their outcome measures , Ti et al, 2004, Grueterich et al, 2002b, Kolli et al, 2010. This chapter provides a general update on LSCD pathogenesis, the key role of stem cells and their niche in maintaining corneal homeostasis and avascularity and a general update on LSCD pathogenesis.…”