**3. Decellularized corneas repopulated with stem cells**

Decellularized corneas comprising intact ECM composition and integrity hold the potential to use as an implant in the same or cross-species. They maintain the native mechanical strength and stromal structure but lack the cellular components, preventing graft rejection, or activating undesirable immune responses. Recently, Polisetti and coworkers explored the use of decellularized human corneas as scaffolds. The decellularized human corneal scaffold preserves the native extracellular matrix proteins, glycosaminoglycans, and tissue structure to allow regeneration of the epithelium and stroma of the host tissue ex-vivo [20]. Decellularized human limbus (DHL) was used as a biomimetic scaffold for transplanting limbal epithelial progenitor cells (LEPCs) in ex-vivo transplantation. The scaffold provided a limbal niche-specific microenvironment where native ECM composition was preserved and showed excellent biocompatibility for LEPCs and limbal melanocytes (LMS). Furthermore, the scaffold allowed complete epithelization with interspersed melanocytes and stromal repopulation from host tissue, thereby showing potential for regeneration of damaged cornea in patients suffering from limbal stem cell deficiency (LSCD) [21].

A rabbit corneal model was used to study the in-vivo biocompatibility of decellularized human corneal stroma with and without recellularization of human adiposederived adult stem cells (h-ADASC). The decellularized corneal sheets had intact extracellular matrices and an excellent recellularization capacity with h-ADASC. In addition, it revealed good transparency with no clinical sign of rejection. The postmortem analysis revealed the survival of transplanted stem cells within the graft and the differentiation of stem cells into functional keratocytes [22].

In a human clinical trial, decellularized porcine corneal stromas were transplanted into 47 patients with corneal fungal infection. There was no recurrent disease observed within 3 years of the study. Seventy-two percent of patients showed visual improvement. However, neovascularization was observed in 53% of patients but was suppressed eventually. Thus, the decellularized cornea has demonstrated promising potential in regenerating damaged corneas while preserving the native ECM composition. However, care must be taken to prevent zoonotic pathogenic transmission, as seen in recent years of global transmission of coronavirus from animals to humans.
