Progress in multiple genetically modified minipigs for xenotransplantation in China

Journal Article · 18 February 2019 · Xenotransplantation

DOI: https://doi.org/10.1111/xen.12492 · OSTI ID:1494959

Pan, Dengke ^[1]; Liu, Ting ^[2]; Lei, Tiantian ^[2]; Zhu, Huibin ^[3]; Wang, Yi ^[4]; Deng, Shaoping ^[1]

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1. Organ Transplant and Clinical Immunology Translational Medicine Key Laboratory of Sichuan Province Sichuan Academy of an Transplant Science &, Sichuan Provincial People’s Hospital Chengdu China
2. School of Medicine University of Electronic Science and Technology of China Chengdu China
3. Chengdu Clonorgan Biotechnology Co., LTD Chengdu China
4. Health Management Center Sichuan Academy of Medical Science &, Sichuan Provincial People’s Hospital Chengdu China

Abstract Pig‐to‐human organ transplantation provides an alternative for critical shortage of human organs worldwide. Genetically modified pigs are promising donors for xenotransplantation as they show many anatomical and physiological similarities to humans. However, immunological rejection including hyperacute rejection (HAR), acute humoral xenograft rejection (AHXR), immune cell–mediated rejection, and other barriers associated with xenotransplantation must be overcome with various strategies for the genetic modification of pigs. In this review, we summarize the outcomes of genetically modified and cloned pigs achieved by Chinese scientists to resolve the above‐mentioned problems in xenotransplantation. It is now possible to knockout several porcine genes associated with the expression of sugar residues, antigens for (naturally) existing antibodies in humans, including GGTA1, CMAH, and β4GalNT2, and thereby preventing the antigen‐antibody response. Moreover, insertion of human complement‐ and coagulation‐regulatory transgenes, such as CD46, CD55, CD59, and hTBM, can further overcome effects of the humoral immune response and coagulation dysfunction, while expression of regulatory factors of immune responses can inhibit the adaptive immune rejection. Furthermore, transgenic strategies have been developed by Chinese scientists to reduce the potential risk of infections by endogenous porcine retroviruses (PERVs). Breeding of multi‐gene low‐immunogenicity pigs in China is also presented in this review. Lastly, we will briefly mention the preclinical studies on pig‐to‐non‐human primate xenotransplantation conducted in several centers in China.

• Sponsoring Organization: USDOE
• OSTI ID: 1494959
• Journal Information: Xenotransplantation, Journal Name: Xenotransplantation Journal Issue: 1 Vol. 26; ISSN 0908-665X
• Publisher: Wiley-BlackwellCopyright Statement
• Country of Publication: Country unknown/Code not available
• Language: English