R E V I E W Cultivated limbal stem cell transplantation for ocular surface reconstruction Sanghamitra Burman Virender Sangwan Cornea and Anterior Segment Service, LV Prasad Eye Institute, Hyderabad, India Correspondence: Sanghamitra Burman Cornea and Anterior Segment Service, LV Prasad Eye Institute, Rd no 2, Banjara Hills Hyderabad – 500034, India Tel +91 40 3061 2623/632 Fax +91 40 2354 8271 Email sanghamitra@lvpei.org Abstract: Severe damage to cell repair mechanisms of the limbal region can lead to many disorders such as vascularized conjunctivalization, keratinization, corneal scarring, and corneal opaciﬁcation, collectively described as limbal stem cell deﬁciency (LSCD). Limbal stem cell deﬁciency may occur as a result of depletion of stem cells or destruction of their stromal niche. In such cases, apart from conventional corneal transplantation, limbal stem cell transplantation would be needed to restore vision. Limbal stem cells may be replenished by autologous limbal transplants from the healthy fellow eye in unilateral cases, and allografts from living related donors or cadaveric donors in bilateral cases. The induction of iatrogenic LSCD and its sequelae in donor eyes have motivated researchers to cultivate sheets of limbal epithelium ex vivo, from small fragments of donor tissue for the purpose of ocular surface reconstruction. Keywords: cultivated limbal transplantation, stem cell deﬁciency Introduction The integrity of the self-renewing corneal epithelium relies on the existence of stem cells, which are located in the limbal basal layer (Sun and Green 1977). These limbal stem cells are supported by a unique stromal microenvironment: the stem cell niche (Watt and Hogan 2000). Destructive loss of limbal stem cells or dysfunction of their stromal niche causes what is clinically referred to as limbal stem cell deﬁciency, characterized by conjunctivalization of the cornea, vascularization, chronic inﬂamma- tion, and persistent epithelial defects (Dua et al 1994). Severe ocular surface disease resulting from LSCD as in chemical injury, Stevens-Johnson syndrome (SJS) and ocular cicatricial pemphigoid are devastating conditions that represent a major clinical challenge. Conventional corneal transplants alone in these conditions are destined to fail. Ocular surface reconstruction by means of amniotic membrane transplantation and limbal transplantation has been effective to some extent. More recently cultivated limbal stem cell transplantation, which is the focus of this review, has been shown to be a promising treatment modality in the management of severe limbal stem cell deﬁciency (Pellegrini et al 1997; Koizumi et al 2001b; Sangwan et al 2006). Limbal stem cells Stem cells are deﬁned by their capacity of unlimited or prolonged self-renewal that can produce at least one type of highly differentiated progeny (Grueterich et al 2003). The stem cells of the corneal epithelium are located in the limbal basal layer and are the ultimate source of corneal epithelial renewal (Sun and Green 1977). Cotsarelis and colleagues (1989) conﬁrmed the presence of a small subpopulation of slow-cy- cling limbal basal stem cells that had a signiﬁcant reserve capacity and proliferative response to wounding. Limbal stem cells have a long life span with a slow cell cycle with low mitotic activity under the normal steady state. Limbal stem cells are supported by a unique Clinical Ophthalmology 2008:2(3) 489–502 © 2008 Dove Medical Press Limited. All rights reserved 489