Xenotransplantation in the 21st Century

Abstract

Xenotransplantation, i.e. transplantation across species, is increasingly being viewed a potential solution to the problem of severe shortage of transplant donors. Clinical application of xenotransplantation is, however, limited in large part by the pre-eminent hurdle of the immune response of the recipient against the graft. This immunologic reaction is mediated initially by natural xenoreactive antibodies, complement and natural killer cells, and later by elicited humoral and cellular immune responses that ultimately lead to graft failure. Progress in understanding the cellular and molecular basis of xenograft rejection has characterized the past few years. Additional hurdles to xenotransplantation include physiologic incompatibility of the transplant and the risk of infections. The recent development of novel strategies to overcome xenograft rejection has brought about great optimism that xenotransplantation may be attainable in the near future.

Appropriate Donor Size for Porcine Liver Xenotransplant

“…15 Treatment is further limited by the possibility of transmitting new infectious agents from the graft into the recipient. 3,6 A particular concern has been raised because the transfer of porcine endogenous retroviruses, as a part of pigs' genome, has shown to be acceptable with a xenograft. 5,25,26 The associated risk of this infection, in principal, may be lower in xenotransplant than allotransplant, because it is possible to screen the donor for infectious agents and to eliminate it from the source of the graft.…”

“…2 However, the number of patients requiring liver transplant far outweighs the availability of suitable graft. 3 Also, an increasing number of patients, being referred for liver transplant, have created a crisis in donor organ availability. 4,5 Despite performing many educational efforts by the public and the media during recent years, deceased-donor organ donation has not increased substantially during the past several years and it is unlikely that the supply of donor organs could achieve a level to meet demands.…”

“…Although xenotransplant has this potential to be an optimal solution for organ shortage, as it could provide an unlimited supply of organs, 11 many studies have shown that using animals for human transplant have many clinical limitations at this moment, such as hyperacute rejection, physiologic incompatibility, and the risk of transmission of infection. 3 Before all the mentioned problems, one question should be answered: What are the surgical difficulties owing to size mismatch? Regarding this, from the technical point of view, the size of the liver, length, and diameter of vessels, as well as the discrepancy of the bile duct size, could be a challenge for transplant surgeons.…”

Perspectives on the clinical utility of allografts for bone regeneration within osseous defects: a narrative review

“…9 Although there has been a recent concerted effort to improve the biocompatability of xenografts, [10][11][12] significant risks remain including pathogen transmission, immunogenic rejection, prolonged graft integration, and fracture. [13][14][15] Despite these risks, xenografts continue to be utilized on a limited basis for the treatment of osseous defects primarily because of their abundant supply and their satisfactory osteoconductive characteristics.…”

New Strategies for Acute Liver Failure: Focus on Xenotransplantation Therapy

“…Xenotransplants to animal models using livers detected even 10 years after exposure (43). Another study with 13 recipients of embryonic porcine mesenceobtained from pigs expressing human complement regulatory proteins (5,11), whose organs are protected phalic tissue or extracorporeal perfusion with transgenic pig livers also found no evidence of porcine endogenous against the recipient's complement system, or from pigs that have the α1,3-galactosltransferase gene disrupted retroviruses (PERV) sequences by PCR testing peripheral blood mononuclear cells (44). and, therefore, do not express α1,3Gal (26), demonstrated longer xenograft survival (10).…”