异种肝移植手术的特点与难点
DOI: 10.3969/j.issn.1001-5256.2022.10.002
利益冲突声明:所有作者均声明不存在利益冲突。
作者贡献声明:李霄负责文献检索,撰写论文;陶开山负责指导撰写文章并最终定稿。
-
摘要: 随着基因编辑技术的快速发展,以猪为供体的异种移植越来越接近临床实用。目前猪的心脏和肾脏在非人灵长类动物体内已实现长期存活,进行了初步的临床尝试并取得成功。而异种肝移植最长存活近1个月,也初步具备进入临床试验的条件。但与心脏和肾脏肝移植相比,异种肝移植因手术技术难度高、围手术期管理困难等原因,目前全世界仅有少数中心能够开展。本文试就目前已开展的异种肝移植术式进行综述,并分析其技术特点和难点,为未来开展此类手术试验提供经验与参考。Abstract: The rapid development of gene editing technology showed usefulness of pig xenotransplantation as a donor in clinical application. Clinical trials of non-human primates using pig heart and kidney were able to survive them for a long period of time, while the longest survival of xenograft liver transplantation was nearly 1 month, which could meet the conditions for entering clinical trials for human patients. However, compared with heart and kidney transplantation, only a few units in the world can carry out xenograft liver transplantation due to the high technical difficulty and difficult perioperative management. This review summarized the advancement and progress in the field and discussed the technical characteristics and difficulties, so as to provide experience and reference for the future development of clinical trials, i.e., comparison of pig and liver anatomy, animal models of xenograft liver transplantation, and characteristics and difficulties in liver xenotransplantation technique.
-
[1] MONTGOMERY RA, STERN JM, LONZE BE, et al. Results of two cases of pig-to-human kidney xenotransplantation[J]. N Engl J Med, 2022, 386(20): 1889-1898. DOI: 10.1056/NEJMoa2120238. [2] BENDER M, LÄNGIN M, REICHART B, et al. Overcoming perioperative inflammation as a hurdle for successful preclinical orthotopic cardiac xenogeneic transplantations - particular in regard of the mandatory use of heart-lung machines[J]. Xenotransplantation, 2022, 29(3): e12749. DOI: 10.1111/xen.12749. [3] PIERSON RN 3rd. Progress toward pig-to-human xenotransplantation[J]. N Engl J Med, 2022, 386(20): 1871-1873. DOI: 10.1056/NEJMp2118019. [4] KOZLOV M. Clinical trials for pig-to-human organ transplants inch closer[J]. Nature, 2022, 607(7918): 223-224. DOI: 10.1038/d41586-022-01861-2. [5] ZHANG Z, LI X, ZHANG H, et al. Cytokine profiles in Tibetan macaques following α-1,3-galactosyltransferase-knockout pig liver xenotransplantation[J]. Xenotransplantation, 2017, 24(5): e12321. DOI: 10.1111/xen.12321. [6] ZHANG X, WANG Q, ZHAO 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. [7] WANG Y, LEI T, WEI L, et al. Xenotransplantation in China: Present status[J]. Xenotransplantation, 2019, 26(1): e12490. DOI: 10.1111/xen.12490. [8] ZHANG X, WANG L, ZHANG HT, et al. Preliminary report of preclinical trial of multi-genome engineering pig-to-macaque heart, liver and kidney transplantation[J]. Ogran Transplant, 2021, 12(1): 51-56. DOI: 10.3969/j.issn.1674-7445.2021.01.008.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. [9] KHAJANCHEE YS, JOHNSTON WC, CASSERA MA, et al. Characterization of pancreaticojejunal anastomotic healing in a porcine survival model[J]. Surg Innov, 2017, 24(1): 15-22. DOI: 10.1177/1553350616674638. [10] NTONAS A, KATSOURAKIS A, GALANIS N, et al. Comparative anatomical study between the human and swine liver and its importance in xenotransplantation[J]. Cureus, 2020, 12(7): e9411. DOI: 10.7759/cureus.9411. [11] SHAH JA, NAVARRO-ALVAREZ N, DEFAZIO M, et al. A bridge to somewhere: 25-day survival after pig-to-baboon liver xenotransplantation[J]. Ann Surg, 2016, 263(6): 1069-1071. DOI: 10.1097/SLA.0000000000001659. [12] SHAH JA, PATEL MS, ELIAS N, et al. Prolonged survival following pig-to-primate liver xenotransplantation utilizing exogenous coagulation factors and costimulation blockade[J]. Am J Transplant, 2017, 17(8): 2178-2185. DOI: 10.1111/ajt.14341. [13] KIM K, SCHUETZ C, ELIAS N, et al. Up to 9-day survival and control of thrombocytopenia following alpha1,3-galactosyl transferase knockout swine liver xenotransplantation in baboons[J]. Xenotransplantation, 2012, 19(4): 256-264. DOI: 10.1111/j.1399-3089.2012.00717.x. [14] JI H, LI X, YUE S, et al. Pig BMSCs transfected with human TFPI combat species incompatibility and regulate the human TF pathway in vitro and in a rodent model[J]. Cell Physiol Biochem, 2015, 36(1): 233-249. DOI: 10.1159/000374067. [15] YEH H, MACHAIDZE Z, WAMALA I, et al. Increased transfusion-free survival following auxiliary pig liver xenotransplantation[J]. Xenotransplantation, 2014, 21(5): 454-464. DOI: 10.1111/xen.12111. [16] LAMM V, EKSER B, VAGEFI PA, et al. Bridging to allotransplantation-is pig liver xenotransplantation the best option?[J]. Transplantation, 2022, 106(1): 26-36. DOI: 10.1097/TP.0000000000003722. [17] CARITHERS RL Jr. Liver transplantation: will xenotransplantation be the answer to the donor organ shortage?[J]. Trans Am Clin Climatol Assoc, 2020, 131: 270-285. [18] Group of Organ Transplantation Branch of Chinese Medical Association. Clinical research guidance for xenotransplantation (2018 recommended edition)[J]. Ogran Transplant, 2018, 9(6): 405-408. DOI: 10.3969/j.issn.1674-7445.2018.06.001.中华医学会器官移植学分会异种移植学组. 异种移植临床研究指导意见(2018建议版)[J]. 器官移植, 2018, 9(6): 405-408. DOI: 10.3969/j.issn.1674-7445.2018.06.001. [19] LI X, WANG Y, YANG H, et al. Liver and hepatocyte transplantation: What can pigs contribute?[J]. Front Immunol, 2021, 12: 802692. DOI: 10.3389/fimmu.2021.802692. [20] NUNES DOS SANTOS RM. Insights into pig liver xenotransplantation[J]. Gastroenterol Hepatol (N Y), 2022, 18(4): 216-218. [21] LICHTENSTEIN GR. Exploring pig-to-human liver xenotransplantation[J]. Gastroenterol Hepatol (N Y), 2022, 18(4): 181. [22] CROSS-NAJAFI AA, LOPEZ K, ISIDAN A, et al. Current barriers to clinical liver xenotransplantation[J]. Front Immunol, 2022, 13: 827535. DOI: 10.3389/fimmu.2022.827535. [23] EZZELARAB M, EKSER B, GRIDELLI B, et al. Thrombocytopenia after pig-to-baboon liver xenotransplantation: where do platelets go?[J]. Xenotransplantation, 2011, 18(6): 320-327. DOI: 10.1111/j.1399-3089.2011.00679.x.
本文二维码
计量
- 文章访问数: 576
- HTML全文浏览量: 117
- PDF下载量: 118
- 被引次数: 0