Human donor organs cannot be successfully preserved by transplanting into pigs
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The available literature indicates that growing human tissues or cells within pig hosts is a subject of active research with some preliminary chimeric successes, but it does not establish a blanket rule that human donor organs cannot be preserved or grown in pigs.
The use of pig derivatives in medicine is forbidden in Islamic law texts, despite the fact that certain applications offer medical advantages. Pigs can be one of the best human organ hosts; therefore, using human–pig chimeras may generate beneficial impact in organ transplantation, particularly in xenotransplantation. In Islam, medical emergencies may allow some pig-based treatments and medical procedures to be employed therapeutically. However, depending on the sort of medical use, emergency situation might differ. Using Islamic legal maxim as bioethical framework, the purpose of this study is to examine the use of pigs for the purpose of human–pig chimeric transplant from the perspective of Islamic bioethics. According to the findings, chimeric organ transplantation using pigs should only be done in emergency situations.
Keywords: Chimera, Organ transplantation, Transplant ethics, Islamic legal maxim, Human–pig organ status released display-pdf yes is-olf no is-manuscript no is-preprint no is-journal-matter no is-scanned no is-retracted no Received 2022 Aug 12; Revised 2022 Oct 23; Accepted 2022 Oct 24; Collection date 2023 Apr. Introduction Pigs are the best hosts for human organs in chimeric organ transplantation due to their organ size similarities, simplicity of genetic editing, and short reproductive time (Loike and Kadish 2018 ; Zhong et al. 2019 ).
Al-Zuhaili added that the Muslim scholars agreed that the impurity of the pig includes meat, bones, blood, fat, fur, and skin even if slaughtered in a lawful (halal) way (Al-Zuhaili 2010 ). As a result, all medical treatments using pigs or their derivatives are prohibited, including the transplantation of human–pig chimeric organs, as contamination with pig derivatives is expected especially from the pig tissues in the organ. Chimeric organs are created from human stem cells and implanted into host animals such as pigs and monkeys (Wu et al. 2017 ; Tan et al. 2021 ).
Therefore, this paper will examine the Islamic bioethics perspective on the use of mixed organs made up of human and pig cells for organ transplantation to help patients who need new organs. Human–Animal Chimera Chimera organs are created for organ transplantation. Human–animal chimera research began in 1969, intended to study human biology (Rygaard and Povlsen 1969 ). However, in 2017, pigs began to be served as a host for human organs to create human–pig chimeras that can be an alternative source of organs for organ transplantation (Wu et al. 2017 ). Chimera organs are produced via blastocyst complementation.
This procedure has been successfully used to create chimeras between mammalian species by Kobayashi, in which earlier, he successfully created a rat’s pancreas in a mouse using rat stem cells (Kobayashi et al. 2010 ). On the other hand, human–animal chimeras are created through the injection of patient stem cells into host animal blastocytes (Lu et al. 2019 ). A chimeric organ can be transplanted to a patient with little to no need for immunosuppressive medications, which lowers the cost of therapy and is more beneficial and significant to be an alternative source of organs (Loike and Kadish 2018 ).
This situation, however, can only be accomplished if the organs created have a majority of patient cells. However, on the other hand, if not adequately regulated, chimeric organ transplantation might have adverse effects such as virus transmission, tumor growth, and immune rejection due to contamination of animal cells (Lu et al. 2019 ; Loike and Kadish 2018 ). In April 2021, Jun Wu’s work successfully created a human–monkey chimera for 20 days until it had to be destroyed due to ethical restrictions. The study was conducted in hope to alleviate the shortage of donated organs for transplantation treatment (Tan et al. 2021 ).
These infectious illnesses, including the SARS virus passed from civet to human, are the source of the pandemic (Huther 2009 ). In addition to stringent control, the best choice is to pick animal species that have not been confirmed to be viral carriers. The misconduct of the animal chosen as the host is likely to become a carrier of the virus and spread it. Therefore, it violates the objectives of Sharia in medicine which is to preserve life because medicine should fulfill the objectives of Sharia especially in protecting life. Lastly, the purity status of organs that combine human and animal cells, such as pigs, remains unclear.
The same legal maxim may be used with human–pig organs since organs blended with human and pig tissue are also forbidden in Islam. However, this treatment can benefit humans. An emergency situation occurs when there is an absence of a suitable human organ host from lawful animal, and the necessity to create organs in an unlawful (haram) animal host such as pig is considered a preferable option. The choice of
According to the situation, emergencies may also include the use of human organs grown in pig hosts as a supply of donor organs. Indeed, it is preferable if the chimeric organ is entirely composed of human cells and is free of pig cells. Additionally, body rejection, xenotransplantation-related adverse effects, and significant health issues should be considered to ensure that the medical intervention chosen is more beneficial than detrimental to the patient (Hassan 2021 ). Thus, the chimeric organ should contain at least 90% human or patient cells to minimize these adverse consequences (Loike and Kadish 2018 ).
CRISPR or any other genetic editing technology also contributes to the reduction of side effects by genetically engineering host pigs to be virus- and symptom-free (Sykes and Sachs 2019 ). As a result, it can be argued that human–pig chimeric organ transplantation has the potential to be a viable option for treating organ injury and should be permitted in emergencies. Although this option is still in its early stages of development, it has demonstrated its potential as a safe therapeutic choice.
Solid organ transplantation remains a life-saving treatment for patients worldwide. Unfortunately, the supply of donor organs cannot meet the current need, making the search for alternative sources even more essential. Xenotransplantation using sophisticated genetic engineering techniques to delete and overexpress specific genes in the donor animal has been investigated as a possible option. However, the use of exogenous tissue presents another host of obstacles, particularly regarding organ rejection. Given these limitations, interspecies blastocyst complementation in combination with precise gene knockouts presents a unique, promising pathway for the transplant organ shortage. In recent years, great advancements have been made in the field, with encouraging results in producing a donor-derived organ in a chimeric host. That said, one of the major barriers to successful interspecies chimerism is the mismatch in the developmental stages of the donor and the host cells in the chimeric embryo. Another major barrier to successful chimerism is the mismatch in the developmental speeds between the donor and host cells in the chimeric embryos. This review outlines 19 studies in which blastocyst complementation was used to generate solid organs. In particular, the genesis of the liver, lung, kidney, pancreas, heart, thyroid, thymus and parathyroids was investigated. Of the 19 studies, 7 included an interspecies model. Of the 7, one was completed using human donor cells in a pig host, and all others were rat–mouse chimeras. While very promising results have been demonstrated, with great advancements in the field, several challenges continue to persist. In particular, successful chimerism, organ generation and donor contribution, synchronized donor–host development, as well as ethical concerns regarding human–animal chimeras remain important aspects that will need to be addressed in future research.
Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( https://creativecommons.org/licenses/by/4.0/ ). Abstract Solid organ transplantation remains a life-saving treatment for patients worldwide. Unfortunately, the supply of donor organs cannot meet the current need, making the search for alternative sources even more essential. Xenotransplantation using sophisticated genetic engineering techniques to delete and overexpress specific genes in the donor animal has been investigated as a possible option.
In particular, successful chimerism, organ generation and donor contribution, synchronized donor–host development, as well as ethical concerns regarding human–animal chimeras remain important aspects that will need to be addressed in future research. Keywords: blastocyst complementation, chimerism, genetic engineering, intra-/interspecies, pluripotent stem cells, porcine, transplantation, xenotransplantation status released display-pdf yes is-olf no is-manuscript no is-preprint no is-journal-matter no is-scanned no is-retracted no Received 2025 Jan 8; Revised 2025 Feb 6; Accepted 2025 Feb 9; Collection date 2025 Feb. 1.
recently demonstrated promising results using human cells in pig embryos. Given their size, pigs represent an attractive option for growing human organs. Matsunari et al. used a Sall1 knockout model. While their first attempt using cloned embryos was unsuccessful, using IVF-derived embryos led to 1 chimeric fetus of 12 with morphologically and histologically normal kidneys, with positive donor-cell expression [ 8 ]. Given the difficulties in synchronizing development, Wang et al. opted to target both Six1 and Sall-1 as knockouts to ensure that a large window in developmental progression was achieved [ 18 ].
They went on to successfully generate chimeric adult pigs, with normal serum glucose levels. The oral glucose tolerance test results were also normal in one of the chimeric pigs. Necropsy of one chimeric pig showed macroscopic normal intestinal organs. While all tissue examined in this study showed donor-derived cells, the progeny sired by the chimeric male pigs all demonstrated an apancreatogenic phenotype, suggesting that the sperm were derived from host, not donor cells. Finally, more recently, Matsunari et al. further continued their work in another pig model [ 8 ].
As such, the successful development of donor endothelial and vascular cells using blastocyst complementation is a field of great interest, even for solid organ generation. Hamanaka et al. successfully generated almost 100% donor-derived vascular endothelial and hematopoietic cells in Flk-1 knockout mice (also known as VEGFR2, vascular endothelial
successfully generated entirely human-derived hemato-endothelial cells in ETV2-null pigs analyzed between embryonic day 17 and 18, an important step for the inter-species generation of hemato-endothelial cells [ 103 ]. Successes in developing hemato-endothelial cells are of great significance and will prove to be important with regards to developing organs with the greatest number of donor-derived cells as possible, an invaluable step to avoid graft rejection when organs are transplanted back into the donor. Successful interspecies chimerism becomes even more evident with more evolutionarily distant donor–host species’ pairs, such as human–mouse and human–pig.
This mouse–mouse stage-matching study demonstrated the importance of matching developmental stages between donor cells and host embryos. The naïve mouse ESCs were more compatible with the early-stage mouse blastocyst and more differentiated donor cells contributed better to later-stage gastrulating embryos where the germ layers were defined. Another study of interspecies chimerism demonstrated that human pluripotent stem cells (PSCs) injected into the E6.5-7 gastrulating mouse embryo successfully contributed to the in vitro cultured chimeric embryo and had cell-type-specific gene expression [ 117 ].
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