Overcoming the barriers to xenotransplantation: prospects for the future

Abstract

Cross-species transplantation

Cloning of Homozygous a1,3-Galactosyltransferase Gene Knock-Out Pigs by Somatic Cell Nuclear Transfer

“…To bring xenotransplantation into clinical application, it is essential to overcome xenograft rejections, such as hyperacute rejection, delayed xenograft rejection, and cellular rejection (Ekser and Cooper, 2010). Genetic modification of pigs by technologies based on SCNT would be the most promising approach to solve these issues.…”

“…To overcome donor shortage in organ transplantation, xenotransplantation using organs of genetically modified pigs has been actively investigated (Ekser and Cooper, 2010). Thus far, the development of genetically modified pigs has mainly focused on overcoming the immune rejection of the xenograft.…”

异种胰岛移植中供体猪的筛选: 现状与进展

“…However, there is a significant loss of the transplanted cells on exposure to fresh recipient blood and heterologous antigen, known as instant blood-mediated inflammatory reaction (IBMIR), as well as subsequent humoral and T-cell response that results in xenorejection of islet grafts (Nilsson, 2008;Ekser and Cooper, 2010). The immunological rejection, which poses negative impacts on islet engraftment and survival, is still a major obstacle for clinical application of pig islet xenotransplantation.…”

“…Transgenic expression of human heme oxygenase-1 (HO-1) can protect pig islet cells from ischemia/ reperfusion injury, and/or acute rejection mediated by inflammatory cytokines (Yeom et al, 2012). Additional pig genetic modification, knocking-out tissue factor (TF) and over-expressing human antithrombotic gene (CD39/thrombomodulin), will certainly prevent the occurrence of IBMIR and coagulation dysfunction (Ekser and Cooper, 2010).…”

Development of sensitive methods for detection of porcine endogenous retrovirus-C (PERV-C) in the genome of pigs

“…Pig to human xenotransplantation is a promising approach to alleviate the shortage of human donor organs (Ekser and Cooper, 2010). Pigs were selected as the most suitable donor animals because of several advantages: (i) similarities in physiology, (ii) they can be modified genetically easily and cloned, (iii) their generation time is relatively short, (iv) their litters are large and (v) their breeding costs are low.…”