STEM CELL THERAPY



Stem Cell Therapy

Stem Cell Therapy

Introduction

Stem cells are defined as relatively undifferentiated cells that have the capacity to self-renew and also generate one or more differentiated daughter cells. This holds true in both the adult and embryo. In the adult, a stem cell will continually replenish lost cells in normal and damaged tissue. Nearly all tissues within an organism originate from stem cells during embryonic development. Positional cues trigger cell fate determination that leads to embryonic growth and morphogenesis. Regional cues promote proliferation and differentiation that result in tissue specialisation. During this time, stem cells generate intermediate progenitor cells whose proliferation and differentiation become more restricted as cell maturation and specialisation progresses. At all times, undifferentiated precursor cells and stem cells are preserved during development, so that stem cells persist into adulthood. Thus the human body has many different types of stem cells existing within it, amongst which are those that reside within the eye.

Corneal Epithelium

The development of the cornea is a terminal inductive event in eye formation, with the corneal epithelium derived from the head surface ectoderm overlying the lens after invagination. The complex multi-layered structure of the cornea allows it to fulfill its role, namely, transparency, refraction, photoprotection and protection of internal ocular structures from the external environment. The outermost corneal epithelium accounts for 10% of corneal depth and is crucial to corneal function. It consists of five to seven layers of cells that are connected by intercellular junctions and embedded into the underlying basement membrane by hemidesmosomes to form a stratified epithelium. The primary source of corneal epithelium is considered to be a population of stem cells, residing in the limbal region, which give rise to transient amplifying cells (TACs) (Dua & Azuaro-Blanco, 2000a and Dua & Azuaro-Blanco, 2000b; Kruse, 1997). These, in turn, divide to give the progressively more differentiated, non-dividing cells of the anterior epithelium. The most superficial cells are sealed together by tight junctions to give a barrier with high electrical resistance and low permeability, which is essential for maintenance of corneal homeostasis.

Importance of limbal stem cells in corneal epithelial cell homeostasis

Not only do stem cells ensure that the corneal epithelium undergoes continual self-renewal, they are also responsible for epithelial tissue repair and regeneration throughout the life of the adult cornea (Daniels, Dart, Tuft, & Khaw, 2001; Dua & Azuaro-Blanco, 2000a and Dua & Azuaro-Blanco, 2000b; Miller, Lavker, & Sun, 1993; Kinoshita et al., 2001; Tseng & Sun, 1989). These stem cells are undifferentiated, slow-cycling cells that self-renew and produce transient amplifying cells which migrate to the corneal epithelium ( Kinoshita, Friend, & Thoft, 1981; Tseng, 1989). As these TACs leave the basal cell layer, they differentiate and eventually slough off as flattened superficial cells from the epithelial surface ( Beebe & Masters, 1996 and Thoft & Friend, 1983). The constant cell shedding is replaced by proliferation of limbal stem cells (LSCs).

Characteristics of limbal basal cells that make them stem cells

LSCs have been localised to the Palisades of Vogt in the corneal ...