Application value of ultrasound in gene-edited pig-monkey xenogeneic heart transplantation

doi:10.3877/cma.j.issn.1672-6448.2024.06.011

Chinese Journal of Medical Ultrasound (Electronic Edition) ›› 2024, Vol. 21 ›› Issue (06): 617-623. doi: 10.3877/cma.j.issn.1672-6448.2024.06.011

• Basic Science Research • Previous Articles Next Articles

Application value of ultrasound in gene-edited pig-monkey xenogeneic heart transplantation

Rong Zhou¹, Yaping Zhang¹, Yu Liao¹, Xiaoping Cheng¹, Yulong Guan², Guangyu Pan³, Jie Yan⁴, Xianzhi Wang⁵, Zhongshan Gou⁶, Dengke Pan⁷, Dianyuan Li⁸^,^†()

^1. Department of Thoracic and Cardiac Surgery, First People's Hospital of Neijiang, Neijiang 641000, China
^2. Extracorporeal Circulation Center, National Cardiovascular Disease Center, Fuwai Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100037, China
^3. Department of Cardiac Surgery, Peking University International Hospital, Beijing 102206, China
^4. Chengdu Aoge Biotechnology Co, Ltd., Chengdu 610094, China
^5. Department of Thoracic and Cardiac Surgery, First People's Hospital of Guangyuan, Guangyuan 628000, China
^6. Center of Cardiovascular Disease, Affiliated Suzhou Hospital of Gusu School, Nanjing Medical University, Suzhou 215000, China
^7. Clinical Immunology Translational Medicine Key Laboratory of Sichuan Province, Affiliated Hospital of Electronic Science and Technology University, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, Chengdu 610072, China
^8. Department of Cardiovascular Surgery, Affiliated Suzhou Hospital of Gusu School, Nanjing Medical University, Suzhou 215000, China

Received:2024-03-21 Online:2024-06-01 Published:2024-08-05
Contact: Dianyuan Li

Abstract

Abstract:

Objective

To assess the application value of ultrasound in gene edited pig-monkey xenogeneic heart transplantation.

Methods

On December 16, 2023, a case of gene-edited pig-monkey heart xenotransplantation was performed in the Institute of Experimental Animals of Sichuan Academy of Medical Sciences and Sichuan People's Hospital. Ultrasound was used to evaluate the size and function of the heart before surgery to assist in the formulation of the transplantation plan, and to monitor the changes of cardiac function and structure, anastomotic blood flow, and general conditions of the whole body after surgery. Spearman correlation was used to analyze the correlation of the thickness of pig heart left ventricular intima (LVEN) and the thickness of pig heart right ventricular intima (RVEN) with IgG and IgM antibodies.

Results

The preoperative evaluation showed that the size and function of donor and recipient hearts were different and the donor and recipient were well matched, suggesting the feasibility of heterotopic cardiac transplantation. After operation, the pig heart and the monkey heart worked together in parallel to maintain the blood circulation of the monkey, and the anastomosis was smooth. The ejection fraction of the monkey heart and the pig heart were maintained at about 60% and 35%, respectively. After operation, the anterior papillary muscle of the mitral valve and the wall of the left and right ventricles of the pig heart gradually thickened (the thickness of the anterior papillary muscle of the mitral valve was 5.4 ~ 8.8 mm, the thickness of the left ventricular wall was 6.0 ~ 8.5 mm, and the thickness of the right ventricular wall was 2.1 ~ 3.5mm), and the ventricular intima of the pig heart also thickened (LVEN: 1.0 ~ 3.1 mm, RVEN: 1.0 ~ 2.8 mm). There was no increase in IgG or IgM antibodies after operation. Correlation analysis showed that there was no significant correlation between IgG/IgM antibodies and the endocardial thickness of the left and right ventricles (P > 0.05).

Conclusion

Gene-edited pigs are feasible as xenotransplantation donors. Ultrasound has good application value for preoperative evaluation, surgical effect evaluation, postoperative management, and immune monitoring of xenografts. Our findings provide strong technical support and data reference for the future clinical application of gene edited pig-monkey xenogeneic heart transplantation.

Key words: Gene edited pigs, Macaca mulatta, Echocardiogram, Xenogenic heart transplantation

Rong Zhou, Yaping Zhang, Yu Liao, Xiaoping Cheng, Yulong Guan, Guangyu Pan, Jie Yan, Xianzhi Wang, Zhongshan Gou, Dengke Pan, Dianyuan Li. Application value of ultrasound in gene-edited pig-monkey xenogeneic heart transplantation[J]. Chinese Journal of Medical Ultrasound (Electronic Edition), 2024, 21(06): 617-623.

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Figures/Tables 7

References 14

1	陈良万, 李虔桢, 戴小福, 等. 心脏移植的发展现状和新挑战[J]. 器官移植, 2023, 14(1): 31-41.
2	Hong SN, Mohiuddin MM, Ananthram M, et al. Longitudinal echocardiogram imaging in the first genetically modified porcine to human cardiac xenotransplant[J]. JACC Cardiovasc Imaging, 2023, 16(4): 553-557.
3	Niu D, Ma X, Yuan T, et al. Porcine genome engineering for xenotransplantation[J]. Adv Drug Deliv Rev, 2021, 168: 229-245.
4	Goerlich CE, Griffith B, Hanna P, et al. The growth of xenotransplanted hearts can be reduced with growth hormone receptor knockout pig donors[J]. J Thorac Cardiovasc Surg, 2023, 165(2): e69-e81.
5	Koh J, Chee HK, Kim KH, et al. Historical review and future of cardiac xenotransplantation[J]. Korean Circ J, 2023, 53(6): 351-366.
6	Griffith BP, Goerlich CE, Singh AK, et al. Genetically modified porcine-to-human cardiac xenotransplantation[J]. N Engl J Med, 2022, 387(1): 35-44.
7	窦科峰, 张玄, 陶开山. 异种移植存在的问题及国内发展现状[J]. 空军军医大学学报, 2024, 45(1): 1-4.
8	Meier RPH, Longchamp A, Mohiuddin M, et al. Recent progress and remaining hurdles toward clinical xenotransplantation[J]. Xenotransplantation, 2021, 28(3): e12681.
9	Garcia LR, Brito FS, Felicio ML, et al. Clinical trials in cardiac xenotransplantation: Are we ready to overcome barriers? [J]. J Card Surg, 2021, 36(10): 3796-3801.
10	Jack C, Hannah C. Heterotopic heart transplantation: technical considerations[M]//Operative techniques in thoracic and cardiovascular surgery: a comparative atlas. Philadelphia: W.B.Saunders, 2017.
11	Sack FU. Surgical technique of heart transplantation: standard procedure or is there room for further development[J]. Transplantationsmedizin, 2010, 22(1): 47.
12	DiChiacchio L, Singh AK, Chan JL, et al. Intra-abdominal heterotopic cardiac xenotransplantation: pearls and pitfalls[J]. Front Cardiovasc Med, 2019, 6: 95.
13	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.
14	Soares C, Hong SN, Hanna P, et al. Abstract 10214: Invasive versus echocardiographic hemodynamics in the first genetically modified porcine to human xenotransplant[J]. Circulation, 2022, 146(Suppl_1): A10214.

类别	LV（mm）	RV（mm）	LA（mm）	RA（mm）	LVPW（mm）	IVS（mm）	RVW（mm）	AO（mm）	AAO（mm）
P-H	13	8	8	10×14	6	6	2	9	9
M-H	23	12	16	16×22	8	8	2	15	13
类别	PA（mm）	LVEN（mm）	RVEN（mm）	APM（mm）	MV（cm/s）	AV（cm/s）	PV（cm/s）	LVEF（%）
P-H	8	1	1	5.5	84/76	116	83	75
M-H	11.5	1	1	6	96/83	164	79	70

类别	LV（mm）	RV（mm）	LA（mm）	RA（mm）	LVPW（mm）	IVS（mm）	RVW（mm）	AO（mm）	AAO（mm）
P-H	13	8	8	10×14	6	6	2	9	9
M-H	23	12	16	16×22	8	8	2	15	13
类别	PA（mm）	LVEN（mm）	RVEN（mm）	APM（mm）	MV（cm/s）	AV（cm/s）	PV（cm/s）	LVEF（%）
P-H	8	1	1	5.5	84/76	116	83	75
M-H	11.5	1	1	6	96/83	164	79	70

指标	正常值	术后0天	术后第3天	术后第7天	术后第9天	术后第16天	术后第20天	术后第28天	术后第34天	术后第40天
IgG	689	1130	971	1165	1045	1070	964	921	887	900
IgM	1344	1448	1655	1111	975	1315	1066	967	1001	975

指标	正常值	术后0天	术后第3天	术后第7天	术后第9天	术后第16天	术后第20天	术后第28天	术后第34天	术后第40天
IgG	689	1130	971	1165	1045	1070	964	921	887	900
IgM	1344	1448	1655	1111	975	1315	1066	967	1001	975

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