Cytolytic assessment of hyperacute rejection and production of nuclear transfer embryos using hCD46-transgenic porcine embryonic germ cells

Jung, Won Seok; Ahn, Kwang Sung; Sorrell, Alice M.; Shin, S T; Heo, Soon Young; Kang, Jee Hyun; Park, Jin-Ki; Chang, Won-Kyong; Shim, Hosup

doi:10.1017/s096719940800511x

Cited by 6 publications

(2 citation statements)

References 49 publications

(66 reference statements)

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“…Utilizing embryonic germ (EG) cells, which unlike somatic cells can proliferate indefinitely while remaining undifferentiated, Hosup Shim ( 53 ) developed a method to create transgenic pigs capable of expressing human CD59. These EG cells, derived from primordial germ cells (PGC) ( 54 ), were genetically modified with a 456 bp fragment of the hCD59 gene, encompassing the entire coding region, obtained from human fibroblast genes ( 55 ). Post-transfection into porcine EG cells ( 56 ), these modified cells exhibited significantly higher mitochondrial activity when exposed to human serum containing complement, compared to non-transgenic controls, demonstrating enhanced survival under HAR conditions.…”

Section: Genetic Modification Of Pigs For Xenotransplantationmentioning

confidence: 99%

Cutting edge of genetically modified pigs targeting complement activation for xenotransplantation

Sun,

Song,

et al. 2024

Front. Immunol.

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In the quest to address the critical shortage of donor organs for transplantation, xenotransplantation stands out as a promising solution, offering a more abundant supply of donor organs. Yet, its widespread clinical adoption remains hindered by significant challenges, chief among them being immunological rejection. Central to this issue is the role of the complement system, an essential component of innate immunity that frequently triggers acute and chronic rejection through hyperacute immune responses. Such responses can rapidly lead to transplant embolism, compromising the function of the transplanted organ and ultimately causing graft failure. This review delves into three key areas of xenotransplantation research. It begins by examining the mechanisms through which xenotransplantation activates both the classical and alternative complement pathways. It then assesses the current landscape of xenotransplantation from donor pigs, with a particular emphasis on the innovative strides made in genetically engineering pigs to evade complement system activation. These modifications are critical in mitigating the discordance between pig endogenous retroviruses and human immune molecules. Additionally, the review discusses pharmacological interventions designed to support transplantation. By exploring the intricate relationship between the complement system and xenotransplantation, this retrospective analysis not only underscores the scientific and clinical importance of this field but also sheds light on the potential pathways to overcoming one of the major barriers to the success of xenografts. As such, the insights offered here hold significant promise for advancing xenotransplantation from a research concept to a viable clinical reality.

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Section: Genetic Modification Of Pigs For Xenotransplantationmentioning

confidence: 99%

Cutting edge of genetically modified pigs targeting complement activation for xenotransplantation

Sun,

Song,

et al. 2024

Front. Immunol.

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“…Won et al. [42] introduced the human complement regulatory protein CD46 into porcine embryonic germ (EG) cells which were resistant against hyperacute rejection and gave rise to CD46‐transgenic embryos. The usefulness of the transgenic approach may be predicted by this cytolytic assessment prior to actual production of transgenic pigs.…”

Section: Donor Pigsmentioning

confidence: 99%

Xenotransplantation literature update: May–October, 2009

Schneider

2009

Xenotransplantation

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In vitro development of porcine transgenic nuclear-transferred embryos derived from newborn Guangxi Bama mini-pig kidney fibroblasts

Liu

Zhu

et al. 2014

In Vitro Cell.Dev.Biol.-Animal

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Porcine transgenic cloning has potential applications for improving production traits and for biomedical research purposes. To produce a transgenic clone, kidney fibroblasts from a newborn Guangxi Bama mini-pig were isolated, cultured, and then transfected with red and green fluorescent protein genes using lipofectamine for nuclear transfer. The results of the present study show that the kidney fibroblasts exhibited excellent proliferative capacity and clone-like morphology, and were adequate for generation of somatic cell nuclear transfer (SCNT)-derived embryos, which was confirmed by their cleavage activity and blastocyst formation rate of 70.3% and 7.9%, respectively. Cells transfected with red fluorescent protein genes could be passed more than 35 times. Transgenic embryos cloned with fluorescent or blind enucleation methods were not significantly different with respect to cleavage rates (92.5% vs. 86.8%, p > 0.05) and blastocyst-morula rates (26.9% vs. 34.0%, p > 0.05), but were significantly different with respect to blastocyst rates (3.0% vs. 13.2%, p < 0.05). Cleavage (75.3%, 78.5% vs. 78.0%, p > 0.05), blastocyst (14.1%, 16.1% vs. 23.1%, p > 0.05) and morula/blastocyst rates (43.5%, 47.0% vs. 57.6%, p > 0.05) were not significantly different between the groups of transgenic cloned embryos, cloned embryos, and parthenogenetic embryos. This indicates that long-time screening by G418 caused no significant damage to kidney fibroblasts. Thus, kidney fibroblasts represent a promising new source for transgenic SCNT, and this work lays the foundation for the production of genetically transformed cloned Guangxi Bama mini-pigs.

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Cytolytic assessment of hyperacute rejection and production of nuclear transfer embryos using hCD46-transgenic porcine embryonic germ cells

Cited by 6 publications

References 49 publications

Cutting edge of genetically modified pigs targeting complement activation for xenotransplantation

Cutting edge of genetically modified pigs targeting complement activation for xenotransplantation

Xenotransplantation literature update: May–October, 2009

In vitro development of porcine transgenic nuclear-transferred embryos derived from newborn Guangxi Bama mini-pig kidney fibroblasts

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