The current state of xenotransplantation

Abstract

Pigs as a source of grafts for xenotransplantation can help to overcome the rapidly growing shortage of human donors. However, in the case of pig-to-human transplantation, the antibody-xenoantigen complexes lead to the complement activation and immediate hyperacute rejection. Methods eliminating hyperacute rejection (HAR) include α1,3-galactosyltransferase (GGTA1) inactivation, regulation of the complement system and modification of the oligosaccharide structure of surface proteins. The humoral immune response control and reduction of the risk of coagulation disorders are the priority tasks in attempts to overcome acute humoral xenograft rejection that may occur after the elimination of HAR. The primary targets for research are connected with the identification of obstacles and development of strategies to tackle them. Because of the magnitude of factors involved in the immune, genetic engineers face a serious problem of producing multitransgenic animals in the shortest possible time.

The potentiating effect of hTFPI in the presence of hCD47 reduces the cytotoxicity of human macrophages

“…20 It has been reported that hCD47-expressing α1,3-galactosyltransferase knockout pigs are promising solutions for xenotransplantation. 21 In this study, hCD47-expressing PK15 cells showed better viability when exposed to activated THP-1 cells than wild-type PK-15 cells. This survival effect was thought to be due to the hCD47: hSIRP-a interaction.…”

Limitations of recellularized biological scaffolds for human transplantation

“…Strategies to prevent such infection include the use of small interfering RNA (Miyagawa et al, 2005) and, more recently, inactivation of PERV by CRISPR-Cas9 technology (Niu et al, 2017). To date, virus transmission following a xenograft is extremely rare, and none have been reported in the past 15 years (Zeyland, Lipinski, & Slomski, 2015). To reduce the risk of infection and consequently the risk of an acellular scaffold producing an immune response, rigid standardized viral tests and genetic modifications to the donor organ should be considered.…”

Pig-to-human xenotransplantation: Overcoming ethical obstacles

“…Additionally, there is also a risk of xenograft organs wearing out or failing prematurely, because pigs typically have a shorter lifespan than humans, that is, 10 -15 years. [19,20] This means that their tissues ARTICLE age at a quicker rate than human tissues. [19] Knowledge on the longevity of xenograft organs in humans is deficient.…”