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Herpesvirus microRNAs for Use in Gene Therapy Immune-Evasion Strategies
Published in Yashwant Pathak, Gene Delivery, 2022
Vineet Mahajan, Shruti Saptarshi, Yashwant Pathak
A paradigm shift is taking place in transplantation medicine, away from traditional chemical immunosuppression regimens that dominate clinics today and leaning toward modalities that are tissue and cell specific. As a result, xenotransplantation is sure to become a less debated issue in the coming years, and a greater challenge for clinicians, transplant immunologists, and biologists. The ability to deliver exogenous nucleic acids to cells of various tissues is the basis for a successful use of gene therapy in transplantation.
Medicolegal aspects of death
Published in Jason Payne-James, Richard Jones, Simpson's Forensic Medicine, 2019
Jason Payne-James, Richard Jones
Xenotransplantation is the transplantation of living cells, tissues or organs from one species to another. Such cells, tissues or organs are called xenografts or xenotransplants. Advances in xenotransplantation have the potential to resolve the issue of organ shortages. Organs or tissue such as heart valves, corneas, hearts and kidneys have been explored for potential as xenografts. However, such procedures may meet with a degree of concern from the public. Grafting of animal tissue into humans has always seemed tempting and clinical trials have been performed with some success. But there is, for example, considerable difficulty with cross-matching the tissues and considerable concern about the possibility of transfer of animal viruses to an immunocompromised human host. Strains of donor animals, usually pigs, are being bred in clinically clean conditions to prevent viral contamination, but there is still no guarantee of a close or ideal tissue match. There has also been an increasing interest in the development of patient-derived xenograft (PDX) models where human tumours are xenotransplanted into immunocompromised mice and such models act as translational tools in preclinical studies of cancer treatments. It is essential that clear protocols are in place for the study of the many aspects of xenotransplantation and for the introduction of such xenografts into the clinical setting. Such protocols must take into account the variable religious and cultural sensitivities which will influence individuals’ perception of such practices.
Connecting lines from a medical point of view
Published in Elisabeth Hildt, Dietmar Mieth, In Vitro Fertilisation in the 1990s, 2018
While no research on GLGT is being carried out in humans, transgenic animals are steadily gaining importance in medicine and animal breeding. Transgenic animals are living creatures in which, by methods of genetic recombination, a foreign gene has been implanted or an own gene has been destroyed (‘knocked out’) or modified. They are produced as models in order to obtain an insight into complex biological networks or into the nature of certain inherited diseases. They are also used for the toxicological testing of new drugs and other substances, and for the production of human proteins (‘gene pharming’). Finally, it is expected that transgenic pigs will provide human-compatible organs for xenotransplantation. The experience gathered with such animal experiments can probably be transferred to humans and is likely to influence the discussion on human germline gene therapy. PID after such therapy – if ever accepted – could well become mandatory.
Bioengineering strategies for nephrologists: kidney was not built in a day
Published in Expert Opinion on Biological Therapy, 2020
Anna Julie Peired, Benedetta Mazzinghi, Letizia De Chiara, Francesco Guzzi, Laura Lasagni, Paola Romagnani, Elena Lazzeri
In particular, these regimens are heavier than the ones used for allotransplants, increasing the risk of recipient death, or involve drugs not yet tested on humans [22]. This aspect is being improved thanks to the latest advances in genome editing, in particular, the CRISPR/Cas9 approach, which, applied to xenotransplantation, have considerably sped progress toward clinical relevance, as reviewed elsewhere [23]. Briefly, a whole panel of genes vital to improving xenograft survival rate have been modified using this technique, including cytidine monophosphate-N-acetylneuraminic acid hydroxylase, B1,4N-acetylgalactosaminyltransferase, isoglobotrihexosylceramide synthase, class I MHC, von Willebrand factor and C3. The risk of transmission of a porcine infectious disease to the recipient, and subsequent health and legal issues, is another problem faced by xenotransplantation. Particular concerns involve porcine endogenous retroviruses (PERVs), which are integrated into the pig genome and are present within all transplanted tissues, but have shown no human transmission so far [22,24]. However, PERVs can be inactivated using CRISPR-Cas9 [25] or by currently available anti-retroviral drugs [26], bringing clinical trials a step closer.
Patient and family expectations of beta-cell replacement therapies in type 1 diabetes
Published in Islets, 2018
Akitsu Kawabe, Shinichi Matsumoto, Masayuki Shimoda
XIT is islet transplantation from other animals, commonly pigs, to humans. XIT would resolve many of the difficulties associated with AIT, including immediate availability and unlimited supply of islets. However, xenografts are associated with immunological rejection and potential risk of the transmission of viral infections. Accordingly, research and clinical applications using islets derived from designated pathogen-free pigs with an immunoisolating membrane or hydrogel have proceeded to minimize the infection risk and prevent immunological rejection. Some clinical trials have already been conducted to assess the effect and safety of clinical pig XIT.19,20 These trials indicated a certain effect, such as the reduction of unaware hypoglycemia events in unstable T1DM patients; in addition, no transmission of retroviruses and microorganisms was reported. Conversely, because the current encapsulation technology may deteriorate islet function, the main endpoint of achieving insulin-free status has not yet been reached. In this survey, XIT was well accepted and was the second choice option after IPS. Patients reportedly prefer to receive a new organ from a donor of the same species, especially under circumstances in which a human organ was supposed to be unavailable.21,22 Accurate information about xenotransplantation could help patients to accept these treatments. In our present survey, the advantages of XIT, such as its greater availability, might have appealed to the respondents.
Spermatogonial stem cell transplantation and male infertility: Current status and future directions
Published in Arab Journal of Urology, 2018
Connor M. Forbes, Ryan Flannigan, Peter N. Schlegel
Xenotransplantation, where cells from one species are transplanted into the microenvironment of another species, remains a useful tool in the growth of SSCs. The first documented occurrence of SSC xenografting from humans occurred in 2002, when preparations from testis biopsies of six infertile men were injected into the rete testis of nude mice [36]. These were found to survive for up to 6 months in the host testes, albeit in severely decreased numbers, and without assaying their function [36]. This has been successfully replicated with rat, rabbit, and baboon testis tissue, which has been successfully induced to propagate when transplanted into the rete testis of nude mice [31]. In addition, pig and goat testicular tissue has been able to undergo spermatogenesis in mouse xenografts [37].