Downregulation of Gabarapl1 significantly attenuates antibody binding to porcine aortic endothelial cells

Xie, Chengyu; Qu, Zepeng; Hara, Hidetaka; Dai, Wenjie; Wang, Xiliang; Pan, Dengke; Zhou, Ming; Dai, Yifan; Cai, Zhiming; Zhang, Junfang; Cooper, David K. C.; Mou, Lisha

doi:10.1111/xen.12537

Cited by 2 publications

(2 citation statements)

References 21 publications

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“…Xie et al. succeeded in alleviating antibody-mediated rejection using Gabarapl1 knockdowns in primary porcine aortic endothelial cells (PAECs) ( 238 ). While in another pre-clinical trial, the inhibition of COX-2 expression decreased PAECs death from 20% to 7% after 2 hours, making COX-2 inhibitors a candidate for therapeutic targeting to protect vascular endothelial cells in xenotransplantation ( 43 ).…”

Section: The Prevention Of Xenotransplantation Rejectionmentioning

confidence: 99%

Current status of xenotransplantation research and the strategies for preventing xenograft rejection

Zhou

Wang

et al. 2022

Front. Immunol.

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Transplantation is often the last resort for end-stage organ failures, e.g., kidney, liver, heart, lung, and pancreas. The shortage of donor organs is the main limiting factor for successful transplantation in humans. Except living donations, other alternatives are needed, e.g., xenotransplantation of pig organs. However, immune rejection remains the major challenge to overcome in xenotransplantation. There are three different xenogeneic types of rejections, based on the responses and mechanisms involved. It includes hyperacute rejection (HAR), delayed xenograft rejection (DXR) and chronic rejection. DXR, sometimes involves acute humoral xenograft rejection (AHR) and cellular xenograft rejection (CXR), which cannot be strictly distinguished from each other in pathological process. In this review, we comprehensively discussed the mechanism of these immunological rejections and summarized the strategies for preventing them, such as generation of gene knock out donors by different genome editing tools and the use of immunosuppressive regimens. We also addressed organ-specific barriers and challenges needed to pave the way for clinical xenotransplantation. Taken together, this information will benefit the current immunological research in the field of xenotransplantation.

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Section: The Prevention Of Xenotransplantation Rejectionmentioning

confidence: 99%

Current status of xenotransplantation research and the strategies for preventing xenograft rejection

Zhou

Wang

et al. 2022

Front. Immunol.

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“…Using a similar approach to deplete MHC expression, Xie et al aimed to alleviate acute and chronic antibody‐mediated rejection using Gabarapl1 (or GABA type A receptor‐associated protein like 1) knockdowns, a non‐Gal antigen, in primary porcine aortic endothelial cells (PAECs) . It was hypothesized that Gabarapl1 knockdowns could decrease the expression of human leukocyte antigen (HLA) class II and MHC and thus alleviating acute and chronic antibody‐mediated rejection.…”

Section: Improving Xenograft Outcomes Through Genetic Modificationsmentioning

confidence: 99%

Xenotransplantation literature update, November/December 2019

Thomas

Hawthorne

Burlak

2020

Xenotransplantation

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The ever-increasing disparity between the lack of organ donors and patients on the transplant waiting list is increasing worldwide. For the past several decades xenotransplantation has led the way to correct this deficit and remains clearly the only feasible option to provide a means to meet the demand for patients in need of an organ transplant. Xenotransplantation's ability to provide a specifically designed unlimited supply of organs, suited to treat the various needs for transplant organs and cells, has recently been championed by successful pre-clinical trials that have run long-term in non-human primate studies.In this review we show how these improvements have come about due to longterm dedicated research and recent advances in biomedical engineering technology, such as genome editing tools including zinc finger nucleases, TALEN, and CRISPER/ Cas9 which have paved the way for significant breakthroughs in improving xenograft outcomes through genetic modifications to the donor source pig. Other novel approaches include the development of decellularized porcine tissue, such as corneas which can now be transplanted into patients with the minimal need for immunosuppression or other side effects. Further genetic variants of the porcine genome are also now being optimized to abrogate rejection. The emergence of new modalities such as; mesenchymal stem cells, donor thymic vascularization, in vivo bioreactors, chemokine and cytokine therapies have come to show improvements in xenograft outcomes. Furthermore, new studies confirm the safety status of using porcine xenografts, verifying that with current technologies and approaches, the issue of PERV transmission is a moot point. These breakthroughs and technological advancements push the reality of xenotransplantation one step closer to the clinic. K E Y W O R D S complement regulation, CRISPR, Mesenchymal stem cells, zoonosis

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Downregulation of Gabarapl1 significantly attenuates antibody binding to porcine aortic endothelial cells

Cited by 2 publications

References 21 publications

Current status of xenotransplantation research and the strategies for preventing xenograft rejection

Current status of xenotransplantation research and the strategies for preventing xenograft rejection

Xenotransplantation literature update, November/December 2019

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