The Human Tissue-Engineered Cornea (hTEC): Recent Progress

Abstract

Each day, about 2000 U.S. workers have a job-related eye injury requiring medical treatment. Corneal diseases are the fifth cause of blindness worldwide. Most of these diseases can be cured using one form or another of corneal transplantation, which is the most successful transplantation in humans. In 2012, it was estimated that 12.7 million people were waiting for a corneal transplantation worldwide. Unfortunately, only 1 in 70 patients received a corneal graft that same year. In order to provide alternatives to the shortage of graftable corneas, considerable progress has been achieved in the development of living corneal substitutes produced by tissue engineering and designed to mimic their in vivo counterpart in terms of cell phenotype and tissue architecture. Most of these substitutes use synthetic biomaterials combined with immortalized cells, which makes them dissimilar from the native cornea. However, studies have emerged that describe the production of tridimensional (3D) tissue-engineered corneas using untransformed human corneal epithelial cells grown on a totally natural stroma synthesized by living corneal fibroblasts, that also show appropriate histology and expression of both extracellular matrix (ECM) components and integrins. This review highlights contributions from laboratories working on the production of human tissue-engineered corneas (hTECs) as future substitutes for grafting purposes. It overviews alternative models to the grafting of cadaveric corneas where cell organization is provided by the substrate, and then focuses on their 3D counterparts that are closer to the native human corneal architecture because of their tissue development and cell arrangement properties. These completely biological hTECs are therefore very promising as models that may help understand many aspects of the molecular and cellular mechanistic response of the cornea toward different types of diseases or wounds, as well as assist in the development of novel drugs that might be promising for therapeutic purposes.

Generation of a Biomimetic Substitute of the Corneal Limbus Using Decellularized Scaffolds

“…In general, these methods make use of different types of biomaterials that can be prepared in the laboratory and subsequently seeded with living cells to generate a tissue substitute [16,17]. In the case of the cornea, several models of bioartificial corneas have been developed [18,19], and some of these models have been clinically evaluated [20][21][22]. Again, these techniques need to be significantly improved to allow the efficient reproduction of the delicate histoarchitecture of these tissues.…”

Contribution of the Transcription Factors Sp1/Sp3 and AP-1 to Clusterin Gene Expression during Corneal Wound Healing of Tissue-Engineered Human Corneas

“…In order to reduce the need for donor corneas, understanding of corneal wound healing and development of an entirely tissue-engineered human cornea (hTECs) is of prime importance. We succeeded in producing two-layer hTECs (epithelium and stroma) made up of primary cultured cells grown on a naturally secreted extracellular matrix that show characteristics very similar to those of the native cornea, including the expression of the epithelial barrier marker ZO-1, the differentiation marker keratins K3/K12, the corneal integrins αvβ6 and α2β1 and integrin subunits β4, α3 and α6 and the subepithelial basement membrane and stromal components laminin V, collagen types I, IV, V and VII, to name a few [9][10][11][12][13]. Over the last 20 years, we used this substitute to study the mechanistic of wound healing [2,9,11,[14][15][16][17][18].…”

Cell therapy in corneal endothelial disease

“…Currently, there are 2 methods for delivering cellbased products, cell injection and tissue-engineered endothelial keratoplasty (TE-EK) [54]. There is an extensive list of bioengineered materials -whether biomaterials or synthetic polymers -that have been investigated for use as a scaffold [54][55][56][57]. These include amniotic membrane, decellularized tissue such as human DM, corneal stroma, lens capsule, porcine or bovine corneal posterior lamellae [58], silk fibroin, gelatin [59,60], hydrogel [61], collagen, chitosan, agarose and poly-e-lysine [55].…”