Table 5.

Comparative characteristics of each regenerative medical approach for a substitute of corneal or limbal allografts.

	Stem cell-based therapy	Xenotransplantation	Bioengineered product
Indication	•LSCD •Stromal scarring •Endothelial cell failure	•Corneal opacity •Endothelial cell failure	•Corneal opacity •Endothelial cell failure
Main Sources	•Autologous- or allologous adult stem cells (limbal epithelial or mucosal epithelial cells) for LSCD •iPS for LSCD, endothelial cell failure •ES for LSCD, endothelial cell failure •MSC for stromal scarring	• Pig - full thickness graft - anterior lamellar graft - posterior lamellar graft	•Stem cells or human corneal cells •Decellularized cornea •Collagen •Polymers
Benefits	•No Immunosuppression •No zoonosis	•No tumorigenicity •Full or partial thickness tissue replacement feasible	•Less Immunosuppression •No zoonosis •Composite partial tissue replacement feasible
Hurdles	•Tumorigenicity •High cost in iPSC & ES generation and differentiation •Limited differentiation of MSC •Low efficiency of iPSC generation •Genetic variability & phenotypic plasticity of ES & iPSC •Cell replacement only (not for the tissue)	•Xenogeneic rejection •Xenozoonosis •High cost in DPF- or GE-pig production and maintenance •Primitive stage of regulatory framework in some countries	•Low or no cell population in biosynthetic tissue or decellularized cornea •Low tensile strength in biosynthetic tissue
Position in clinical pipeline	• Conditioned approval for autologous limbal epithelial cell therapy by EU •Preclinical stages in iPS, ES, and MSC •Clinical outcomes reported in CLET and COMET	•Preclinical stage	• Clinical trial in decellularized cornea & some biosynthetic analogs
Ethical concern	•Major issue about embryo as human •Issue on human cloning	•Major issue on zoonosis •Minor issue on self-identity	•Safety issue when stem cell or viral vector are used

AbbreviationsCLET: cultivated limbal epithelial transplantation, COMET: cultivated oral mucosal epithelial transplantation, DPF: designated pathogen-free, GE: genetically-engineered, ES: embryonic stem cells, EU: European Union, iPS: induced pluripotent stem cells, LSCD: limbal stem cell deficiency, MSC: mesenchymal stem cells.