Corneal xenotransplantation: Where are we standing?
Author
Ho Yoon, Chang
Jin Choi, Hyuk
Kum Kim, Mee
Institutions
Abstract
The search for alternatives to allotransplants is driven by the shortage of corneal donors
and is demanding because of the limitations of the alternatives. Indeed, current progress in
genetically engineered (GE) pigs, the introduction of gene-editing technology by clustered
regularly interspaced short palindromic repeats (CRISPR)-Cas9, and advanced
immunosuppressants have made xenotransplantation a possible option for a human trial.
Porcine corneal xenotransplantation is considered applicable because the eye is regarded
as an immune-privileged site. Furthermore, recent non-human primate studies have shown
long-term survival of porcine xenotransplants in keratoplasty. Herein, corneal immune
privilege is briefly introduced, and xenogeneic reactions are compared with allogeneic
reactions in corneal transplantation. This review describes the current knowledge on special
issues of xenotransplantation, xenogeneic rejection mechanisms, current
immunosuppressive regimens of corneal xenotransplantation, preclinical efficacy and safety
data of corneal xenotransplantation, and updates of the regulatory framework to conduct a
clinical trial on corneal xenotransplantation. We also discuss barriers that might prevent
xenotransplantation from becoming common practice, such as ethical dilemmas, public
concerns on xenotransplantation, and the possible risk of xenozoonosis. Given that the legal
definition of decellularized porcine cornea (DPC) lies somewhere between a medical device
and a xenotransplant, the preclinical efficacy and clinical trial data using DPC are included.
The review finally provides perspectives on the current standpoint of corneal
xenotransplantation in the fields of regenerative medicine.