The potential of genetically engineered pig heart transplantation in infants with complex congenital heart disease

Abstract

There are more than 40 000 infants born with congenital heart disease annually in the USA, or whom >500 would benefit from early heart transplantation. 1 Despite advances in surgical and medical techniques, complex congenital heart disease in infants, particularly single ventricle pathology, continues to be associated with significant mortality and morbidity. 2 Orthotopic heart transplantation (OHTx) offers the best prospect of long-term survival of these patients, but infant mortality on the heart transplant wait-list is higher than for any other solid organ transplant group. 3,4 In recent years, there have been several advances in genetic engineering of pigs to mitigate the vigorous antibody-mediated rejection of a pig heart transplanted into a nonhuman primate (NHP).Heterotopic heart transplants in NHPs (in the abdomen, where they are not supporting the circulation) have functioned for >24 months (Figure 1). 5 Initially, the success of pig OHTx in NHPs was limited, with few reports of long-term survival. [6][7][8] relatively

Current Aspects of Xenotransplantation in Human

“…After the combination, the possible effects are massive interstitial hemorrhage, infarction, necrosis, thrombosis, and deposition of immunoglobulin IgG, IgM, C3, C4d, and platelets [17,18]. Although this type of rejection could not be controlled currently, the development of new immunosuppressive drugs and genetically engineering pigs are still in progress [3,19]. Cellular xenograft rejection is different to the hyperacute reaction and acute vascular rejection as this type of rejection is associated with both whole organ grafts and cellular grafts [10].…”

“…Once xenotransplantation becomes available and reliable, organ shortages which is one of the major problems in the transplantation field will be either mitigated or even solved as the source of organ donated does not need to rely on only humans [39]. This means that the death on the waiting list for transplantation will dramatically decrease as the source of organ donated does not only rely on humans only [3,40]. Furthermore, with access to xenotransplantation, a commonly developing animal donor which is pig, allows the elderly patients to be able to receive the organ that is compatible to them since the donated organ from pig will solve the age limits the transplantation [34].…”

“…The porcine endogenous retrovirus or PERV is a permanent part of the genome in all mammals which means that not only all recipients will be exposed to the virus, but the risk of transferring the virus to the recipient also cannot be minimized by just selecting the animal from strictly controlled herds [24,37,48]. Although the virus cannot replicate itself or cause disease under physiological conditions, the transmission can occur after the cells of the transplanted organ were co-cultured with human cells [3,13].…”

“…Moreover, there is a considerable public health concern on the possible transmission and activation of PERV over the recent years [2,24]. Nowadays, a number of countries such as the USA and the UK already have guidelines for clinical trials with xenotransplantation, while some countries are still far behind [3,48,49]. This also raises concern that countries might take advantage of attracting desperate patients who need transplantation by creating xenotransplantation programs [7,30,47].…”

“…Over the past decade, the demand for donated organs, which are used in transplantation, is increasing significantly all over the world [1,2]. This is due to the improvement in the medical field, the higher chance of success, and the better outcome after the transplantation [3]. However, the number of organs donated are not able to support the increasing demand [4].…”