Towards the use of hydrogels in the treatment of limbal stem cell deficiency

Abstract

Corneal blindness caused by limbal stem cell deficiency (LSCD) is a prevailing disorder worldwide. Clinical outcomes for LSCD therapy using amniotic membrane (AM) are unpredictable. Hydrogels can eliminate limitations of standard therapy for LSCD, because they present all the advantages of AM (i.e. biocompatibility, inertness and a biodegradable structure) but unlike AM, they are structurally uniform and can be easily manipulated to alter mechanical and physical properties. Hydrogels can be delivered with minimum trauma to the ocular surface and do not require extensive serological screening before clinical application. The hydrogel structure is also amenable to modifications which direct stem cell fate. In this focussed review we highlight hydrogels as biomaterial substrates which may replace and/or complement AM in the treatment of LSCD.

Figure 1

The limbal stem cell niche. Corneal stem cells reside in the limbus at the corneoscleral junction between the conjunctiva and the cornea. Epithelial stem cells in the basal region of the limbus regenerate the corneal surface by differentiating into transient amplifying epithelial cells, which give rise to terminally differentiated epithelial cells that populate the suprabasal and superficial layers of the cornea. Damage to the limbal stem cell niche results in LSCD, disrupting regeneration of the corneal epithelium.

Figure 2

The use of a compressed collagen hydrogel for ex vivo expansion of limbal epithelial cells. Collagen is plastically-compressed using a 120 g load. CK3 (A) and CK14 (B) are expressed in LEC (green) expanded on a laminin-coated compressed collagen gel embedded with keratocytes. Cell nuclei are stained with propidium iodide (red). Images represent 3 different experiments from 3 different corneoscleral rims. Scale bar: 50 μm. Reproduced from ref. .

Figure 3

Alginate gels as LEC storage devices. Calcium alginate gel discs (a) with dimensions approximately 19 mm in length and 1.5 mm in depth are viable storage modules for LEC. Images (100× magnification) represent three individual experiments. Data points on bar chart (b) represent the mean (n = 3 ± S.E.M.) number of live cells extracted from alginate gel discs following 1, 3, 5 and 7 day culture periods.