Perioperative Animal Care for Xenotransplantation from Genetically Edited Pigs to Monkeys

doi:10.12300/j.issn.1674-5817.2024.043

Abstract

Abstract:

Objective To discuss the perioperative care and wound protection of xenotransplantation from genetically edited pigs to monkeys, with the goal of improving the success rate of such experimental procedures. Methods From October 2022 to October 2023, perioperative care and wound protection were performed on 7 recipient rhesus monkeys undergoing xenotransplantation of genetically edited pig tissues and organs. Customized wound protective garments were designed based on monkeys' size and surgical area to protect the wounds, alongside meticulous perioperative care. This included preoperative preparation and medication, intraoperative monitoring of physiological indicators and anesthesia management, and postoperative care comprising wound protection, observation and monitoring, and nutritional support. Results All seven monkeys successfully underwent xenotransplantation. With the aid of protective garments and detailed care, all surgical wounds healed by first intention, and postoperative recovery was satisfactory. Conclusion Proper care and wound protection during xenotransplantation from genetically edited pigs to monkeys not only promote wound healing, but also alleviate pain and harm to animals. This has significant implications for advancing experimental research in pig-monkey xenotransplantation and enhancing animal welfare.

Key words: Genetically edited pig, Xenotransplantation, Rhesus monkey, Care, Wound protection device, Laboratory animal welfare

CLC Number:

R-332

ZHU Chan,ZHANG Dongliang,ZHAO Deli,et al. Perioperative Animal Care for Xenotransplantation from Genetically Edited Pigs to Monkeys[J]. Laboratory Animal and Comparative Medicine, 2024, 44(5): 495-501. DOI: 10.12300/j.issn.1674-5817.2024.043.

Figures/Tables 4

Figure 1 Manufacturing process of wound-protective garments for rhesus monkeys during perioperative period of xenotransplantationNote：A, Body measurements of a monkey (the left shows the front of the monkey, the right shows the back of it, unit: cm.) B, Design drawing of the wound-protective clothing. C, Finished suit (this is a basic sample without limb coverage; the left shows the front of the garment, the right with zippers shows the black of it). D, Rhesus monkeys wearing wound-protective clothing after xenograft knee joint transplantation (sample with pants; the left shows the monkey just after surgery, the right shows the monkey a week after surgery).

Table 1 Information of recipient rhesus monkeys undergoing xenotransplantation surgery

编号 Number	性别 Sex	年龄/year Age/year	体重/kg Weight/kg	移植组织或器官Transplanted tissue or organ	手术时长/h Operating time/h	并发症 Complication	存活时间/d Survival time/d	伤口愈合Wound healing
1	雄	8	11.0	肝脏	7.5	无	14	Ⅰ期愈合
2	雄	9	11.2	心脏	4.0	无	20	Ⅰ期愈合
3	雄	10	10.0	肾脏	4.5	无	27	Ⅰ期愈合
4	雄	10	11.4	膝关节	4.0	无	>365	Ⅰ期愈合
5	雄	11	10.6	角膜和皮肤	6.5	无	>365	Ⅰ期愈合
6	雄	12	12.0	颅骨和神经	6.0	无	>365	Ⅰ期愈合
7	雄	15	17.5	全层腹壁组织	8.0	无	13	Ⅰ期愈合

Figure 2 Wound healing of rhesus monkeys after xenogeneic kidney transplantation (abdominal wound)Note：Left, immediately after surgery; Right, 10 days after surgery at the time of removing stitches.

Figure 3 Survival of skin grafts in rhesus monkeys after xenogeneic skin graft transplantationNote：From left to right， they are immediately after surgery， 5 days after surgery， 10 days after surgery， 15 days after surgery and 19 days after surgery.

References 16

1	PATEL M S, LOURAS N, VAGEFI P A. Liver xenotrans-plantation[J]. Curr Opin Organ Transplant, 2017, 22(6):535-540. DOI: 10.1097/MOT.0000000000000459 .
2	STEPHAN A. Organ shortage: can we decrease the demand?[J]. Exp Clin Transplant, 2017, 15():6-9. DOI: 10.6002/ect.mesot2016.L27 .
3	WALTZ E. When pig organs will fly[J]. Nat Biotechnol, 2017, 35(12):1133-1138. DOI: 10.1038/nbt.4027 .
4	ZHOU Q, LI T, WANG K W, et al. Current status of xenotransplantation research and the strategies for preventing xenograft rejection[J]. Front Immunol, 2022, 13:928173. DOI: 10.3389/fimmu.2022.928173 .
5	张玄, 王琳, 张洪涛, 等. 多基因编辑猪-猴心脏、肝脏、肾脏移植临床前研究初步报道[J]. 器官移植, 2021, 12(1):51-56. DOI: 10.3969/j.issn.1674-7445.2021.01.008 .
	ZHANG X, WANG L, ZHANG H T, et al. Preliminary report of preclinical trial of multi-genome engineering pig-to-macaque heart, liver and kidney transplantation[J]. Organ Transplant, 2021, 12(1):51-56. DOI: 10.3969/j.issn.1674-7445.2021.01.008 .
6	孙德明, 李蔚鸥, 王天奇, 等. 实验动物福利伦理审查的标准化与我国新国标解读[J]. 中国比较医学杂志, 2018, 28(10):133-137. DOI: 10.3969/j.issn.1671-7856.2018.10.023 .
	SUN D M, LI W O, WANG T Q, et al. Standardization of ethical review for laboratory animal welfare and interpretation of the new national standards in China[J]. Chin J Comp Med, 2018, 28(10):133-137. DOI: 10.3969/j.issn.1671-7856.2018.10.023 .
7	张冰, 姬鹏飞, 彭岚刚, 等. 基因编辑 "猪-恒河猴"异位心脏异种移植的围术期治疗及管理经验[J]. 中国体外循环杂志, 2023, 21(4):232-236. DOI: 10.13498/j.cnki.chin.j.ecc.2023.04.11 .
	ZHANG B, JI P F, PENG L G, et al. Preclinical treatment procedure and experience of gene-edited pig-Rhesus het-erotopic heart xenotransplantation[J]. Chin J Extracorpor Circ, 2023, 21(4):232-236. DOI: 10.13498/j.cnki.chin.j.ecc.2023.04.11 .
8	白鸽, 李霄, 张虹, 等. 五指山小型猪-藏酋猴异种肝移植的术前检测[J]. 实用器官移植电子杂志, 2018, 6(5):355-358. DOI: 10.3969/j.issn.2095-5332.2018.05.004 .
	BAI G, LI X, ZHANG H, et al. Pre-operative detection of Wuzhishan miniature pig-Tibetan monkey xenotrans-plantation[J]. Pract J Organ Transplant Electron Version, 2018, 6(5):355-358. DOI: 10.3969/j.issn.2095-5332.2018.05.004 .
9	徐西彬, 朱青, 张恩. 电极植入猕猴脑皮层手术的护理实践及探讨[J]. 实验动物与比较医学, 2022, 42(2):166-170. DOI: 10.12300/j.issn.1674-5817.2021.078 .
	XU X B, ZHU Q, ZHANG E. Nursing practice and discussion of electrode implantation into cerebral cortex of Rhesus monkey[J]. Lab Anim Comp Med, 2022, 42(2):166-170. DOI: 10.12300/j.issn.1674-5817.2021.078 .
10	王宏. 实验猕猴在生物医学研究中的福利管理[J]. 生命科学, 2020, 32(7):711-716. DOI: 10.13376/j.cbls/2020089 .
	WANG H. Welfare management of experimental Rhesus monkey in biomedical research[J]. Chin Bull Life Sci, 2020, 32(7):711-716. DOI: 10.13376/j.cbls/2020089 .
11	胡大海, 易南, 朱雄翔. 实用烧伤康复治疗学[M]. 北京: 人民卫生出版社, 2016.
	HU D H, YI N, ZHU X X. Practical burn rehabilitation therapy[M]. Beijing: People's Medical Publishing House, 2016.
12	LU T Y, YANG B C, WANG R L, et al. Xenotransplantation: current status in preclinical research[J]. Front Immunol, 2020, 10:3060. DOI: 10.3389/fimmu.2019.03060 .
13	DENNER J. Virus safety of xenotransplantation[J]. Viruses, 2022,14(9):1926. DOI: 10.3390/v14091926 .
14	ZHANG X, WANG Q C, ZHAO J J, et al. The resurgent landscape of xenotransplantation of pig organs in nonhuman Primates[J]. Sci China Life Sci, 2021, 64(5):697-708. DOI: 10.1007/s11427-019-1806-2 .
15	中国肝移植注册中心, 国家肝脏移植质控中心, 国家人体捐献器官获取质控中心, 等. 中国移植器官保护专家共识(2022中文版)[J]. 中华外科杂志, 2022, 60(5):409-423. DOI: 10.3760/cma.j.cn112139-20220223-00078 .
	China Liver Transplant Registry, National Center for healthcare quality management in liver transplant, National Quality Control Center for Human Donated Organ Procurement, et al. The Chinese expert consensus on organ protection of transplantation(2022 edition)[J]. Chin J Surg, 2022, 60(5):409-423. DOI: 10.3760/cma.j.cn112139-20220223-00078 .
16	KAMBERI S, MEIER R P H. Xenotransplantation literature update March 2021-March 2023[J]. Xenotransplantation, 2023, 30(3): e12805. DOI: 10.1111/xen.12805 .

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