In vitro and in vivo immune assessments of genetically-engineered pig skin grafts in New World (squirrel) monkeys.

IF 3.3 4区 医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL Xenotransplantation Pub Date : 2023-11-01 Epub Date: 2023-10-23 DOI:10.1111/xen.12832
Hidetaka Hara, Jeremy B Foote, Christophe Hansen-Estruch, Mohamed H Bikhet, Huy Q Nguyen, Mariyam Javed, Max Oscherwitz, Dalis E Collins, David Ayares, Takayuki Yamamoto, Timothy W King, David K C Cooper
{"title":"In vitro and in vivo immune assessments of genetically-engineered pig skin grafts in New World (squirrel) monkeys.","authors":"Hidetaka Hara, Jeremy B Foote, Christophe Hansen-Estruch, Mohamed H Bikhet, Huy Q Nguyen, Mariyam Javed, Max Oscherwitz, Dalis E Collins, David Ayares, Takayuki Yamamoto, Timothy W King, David K C Cooper","doi":"10.1111/xen.12832","DOIUrl":null,"url":null,"abstract":"<p><p>Half a million patients in the USA alone require treatment for burns annually. Following an extensive burn, it may not be possible to provide sufficient autografts in a single setting. Genetic manipulations (GM) of pigs offer the possibility of reducing primate humoral and cellular rejection of pig skin xenografts and thus extending graft survival. We compared the survival of skin grafts from pigs with 9-GM with that of autografts and allografts in squirrel monkeys. Monitoring for rejection was by (1) macroscopic examination, (2) histopathological examination of skin biopsies, and (3) measurement of anti-monkey and anti-pig IgM and IgG antibodies. Autografts (n = 5) survived throughout the 28 days of follow-up without histopathological features of rejection. Median survival of allografts (n = 6) was 14 days and of pig xenografts (n = 12) 21 days. Allotransplantation was associated with an increase in anti-monkey IgM, but the anticipated subsequent rise in IgG had not yet occurred at the time of euthanasia. Pig grafts were associated with increases in anti-pig IgM and IgG. In all cases, histopathologic features of rejection were similar. 9-GM pig skin xenografts survive at least as long as monkey skin allografts (and trended to survive longer), suggesting that they are a realistic clinical option for the temporary treatment of burns. Although monkeys with pig skin grafts developed anti-pig IgM and IgG antibodies, these did not cross-react with monkey antigens, indicating that a primary 9-GM pig skin graft would not be detrimental to a subsequent monkey skin allograft.</p>","PeriodicalId":23866,"journal":{"name":"Xenotransplantation","volume":null,"pages":null},"PeriodicalIF":3.3000,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10843142/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Xenotransplantation","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1111/xen.12832","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2023/10/23 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}
引用次数: 0

Abstract

Half a million patients in the USA alone require treatment for burns annually. Following an extensive burn, it may not be possible to provide sufficient autografts in a single setting. Genetic manipulations (GM) of pigs offer the possibility of reducing primate humoral and cellular rejection of pig skin xenografts and thus extending graft survival. We compared the survival of skin grafts from pigs with 9-GM with that of autografts and allografts in squirrel monkeys. Monitoring for rejection was by (1) macroscopic examination, (2) histopathological examination of skin biopsies, and (3) measurement of anti-monkey and anti-pig IgM and IgG antibodies. Autografts (n = 5) survived throughout the 28 days of follow-up without histopathological features of rejection. Median survival of allografts (n = 6) was 14 days and of pig xenografts (n = 12) 21 days. Allotransplantation was associated with an increase in anti-monkey IgM, but the anticipated subsequent rise in IgG had not yet occurred at the time of euthanasia. Pig grafts were associated with increases in anti-pig IgM and IgG. In all cases, histopathologic features of rejection were similar. 9-GM pig skin xenografts survive at least as long as monkey skin allografts (and trended to survive longer), suggesting that they are a realistic clinical option for the temporary treatment of burns. Although monkeys with pig skin grafts developed anti-pig IgM and IgG antibodies, these did not cross-react with monkey antigens, indicating that a primary 9-GM pig skin graft would not be detrimental to a subsequent monkey skin allograft.

查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
新世界(松鼠)猴转基因猪皮移植物的体外和体内免疫评估。
仅在美国,每年就有50万患者需要接受烧伤治疗。大面积烧伤后,可能无法在单一环境中提供足够的自体移植物。猪的基因操作(GM)提供了减少灵长类动物对猪皮肤异种移植物的体液和细胞排斥反应的可能性,从而延长移植物的存活时间。我们比较了9-GM猪皮肤移植物与自体和同种异体松鼠猴皮肤移植物的存活率。通过(1)宏观检查,(2)皮肤活检的组织病理学检查,以及(3)抗猴和抗猪IgM和IgG抗体的测量来监测排斥反应。自体移植物(n=5)在28天的随访中存活下来,没有排斥反应的组织病理学特征。同种异体移植物(n=6)的中位生存期为14天,猪异种移植物(n=12)的中位数生存期为21天。同种异体移植与抗猴IgM的增加有关,但预期的随后IgG的增加在安乐死时尚未发生。猪移植物与抗猪IgM和IgG的增加有关。在所有病例中,排斥反应的组织病理学特征相似。9-GM猪皮异种移植物的存活时间至少与猴皮同种移植物一样长(而且有存活时间更长的趋势),这表明它们是临时治疗烧伤的现实临床选择。尽管移植了猪皮的猴子产生了抗猪IgM和IgG抗体,但这些抗体没有与猴子抗原发生交叉反应,这表明原代9-GM猪皮移植不会对随后的猴皮同种异体移植造成损害。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 去求助
来源期刊
Xenotransplantation
Xenotransplantation 医学-医学:研究与实验
CiteScore
6.80
自引率
15.40%
发文量
58
审稿时长
>12 weeks
期刊介绍: Xenotransplantation provides its readership with rapid communication of new findings in the field of organ and tissue transplantation across species barriers.The journal is not only of interest to those whose primary area is xenotransplantation, but also to veterinarians, microbiologists and geneticists. It also investigates and reports on the controversial theological, ethical, legal and psychological implications of xenotransplantation.
期刊最新文献
Xenotransplantation Literature Update December 2023–June 2024 Hendrik Jan (Henk) Schuurman, MSc, PhD (1950-2024): In Memoriam. Is Allosensitization Detrimental to Pig Organ Xenotransplantation, and Is Xenosensitization Detrimental to Subsequent Organ Allotransplantation? A Debate Organized by the International Xenotransplantation Association (IXA). Intensive Surveillance of Porcine-Rhesus Kidney Xenotransplant Using Different Ultrasound Techniques. Anti-Non-Gal Antibodies Against Porcine Protein Antigens as Barrier to Long-Term Grafting of Xenografts in Humans.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1