31 Day Xeno Lung Recipient Survival - Progress towards the Clinic

Burdorf, Lars; Laird, Christopher; Sendil, Selin; O’Neill, Natalie A.; Zhang, T.; Parsell, Dawn; Tatarov, Ivan; Abady, Zahra; Cerel, Benjamin; Pratts, Shannon; Phelps, Carol J.; Ayares, David; Azimzadeh, A.M.; Pierson, Richard N.

doi:10.1016/j.healun.2019.01.081

Cited by 6 publications

(2 citation statements)

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“…Orthotopic liver from pigs with knock-out of porcine GGTA1 and under immunosuppressive therapy and exogenous human coagulation factors survived for 29 days in the baboon [ 129 ]. In turn, prolonged survival time for orthotopic lungs xenografts (31 days in immunosuppressed baboon recipient) was achieved using multimodified pigs with knock-out of porcine GGTA1 and β4GalNT2 genes and knock-in of human CD46 , CD47 , TM , EPCR , HO1 genes [ 130 ].…”

Section: Xenotransplantationmentioning

confidence: 99%

CRISPR/Cas Technology in Pig-to-Human Xenotransplantation Research

Ryczek

Hryhorowicz

Zeyland

et al. 2021

IJMS

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CRISPR/Cas (clustered regularly interspaced short palindromic repeats linked to Cas nuclease) technology has revolutionized many aspects of genetic engineering research. Thanks to it, it became possible to study the functions and mechanisms of biology with greater precision, as well as to obtain genetically modified organisms, both prokaryotic and eukaryotic. The changes introduced by the CRISPR/Cas system are based on the repair paths of the single or double strand DNA breaks that cause insertions, deletions, or precise integrations of donor DNA. These changes are crucial for many fields of science, one of which is the use of animals (pigs) as a reservoir of tissues and organs for xenotransplantation into humans. Non-genetically modified animals cannot be used to save human life and health due to acute immunological reactions resulting from the phylogenetic distance of these two species. This review is intended to collect and summarize the advantages as well as achievements of the CRISPR/Cas system in pig-to-human xenotransplantation research. In addition, it demonstrates barriers and limitations that require careful evaluation before attempting to experiment with this technology.

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Section: Xenotransplantationmentioning

confidence: 99%

CRISPR/Cas Technology in Pig-to-Human Xenotransplantation Research

Ryczek

Hryhorowicz

Zeyland

et al. 2021

IJMS

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“…Another study reported a prolonged lung xenograft survival of 31 days on a life-supporting model. Such long survival was achieved by using a multi-transgenic lung donors (GTKO/B4GALNT2/CD46/EPCR/ TBM/HO-1/CD47) and immunosuppressive treatments specifically to control IL-8, IL-6 and TNF levels (Burdorf et al, 2018(Burdorf et al, , 2019). In addition, it was recently demonstrated the feasibility to silence SLA expression in the complete porcine lung endothelium.…”

Section: Lungsmentioning

confidence: 99%

Immunogenetics of xenotransplantation

Oliveira

Valdivia

Blasczyk

et al. 2021

Int J Immunogenetics

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Xenotransplantation may become the highly desired solution to close the gap between the availability of donated organs and number of patients on the waiting list. In recent years, enormous progress has been made in the development of genetically engineered donor pigs. The introduced genetic modifications showed to be efficient in prolonging xenograft survival. In this review, we focus on the type of immune responses that may target xeno‐organs after transplantation and promising immunogenetic modifications that show a beneficial effect in ameliorating or eliminating harmful xenogeneic immune responses. Increasing histocompatibility of xenografts by eliminating genetic discrepancies between species will pave their way into clinical application.

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