The research progress in gene modification strategies and perioperative management of cardiac xenotransplantation

doi:10.3877/cma.j.issn.1674-3903.2022.03.011

Abstract

Abstract:

Cardiac xenotransplantation (CXTx) offers a promising development to address the shortage of donor organs for patients with end-stage heart failure and is a viable strategy to alleviate the shortage of donor hearts. The progress of humanized gene modification technology has opened a new chapter for the clinical application of xenotransplantation.The establishment of animal model of cardiac xenotransplantation has explored a feasible technical route to solve the xenorejection reaction and significantly extended the survival time of transplanted organs.This review will discuss the recent research results of ectopic and orthotopic cardiac xenotransplantation, and some relevant data were selected from several prospective preclinical studies for analysis to explore the construction strategy of heterotopic heart transplantation model and the possible optimal treatment plan, to provide reference for clinic.

Key words: Organ transplantation, Xenotransplantation, Antibody-mediated rejection, Alpha-1, 3-galactosyltransferase, Gene editing, Complement regulatory protein

Mingshi Ren, Rong Wang, Mingyan Wang, Liyue Zhang, Nan Cheng, Yuanbin Wu. The research progress in gene modification strategies and perioperative management of cardiac xenotransplantation[J]. Chinese Journal of Transplantation(Electronic Edition), 2022, 16(03): 183-189.

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References 61

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文献	免疫诱导方案	免疫抑制维持方案	其它支持治疗方案	受体存活情况(d)
Kuuaki等^[47]	ATG(50 mg/kg)	抗人CD154单抗(25 mg/kg)	阿司匹林[40 mg(隔日)]	最长存活78
	LoCD2b(1～4 mg/kg)	抗CD40单抗(20～25 mg/kg)	肝素(5～60 U·kg^－1·h^－1)
	胸腺照射(700 cGy)	MMF(25～110 mg/kg)	更昔洛韦(5 mg·kg^－1·d^－1)
	眼镜蛇毒因子(6 mg/d)	甲泼尼龙(4.0～0.5 mg/kg)	左氧氟沙星(10 mg·kg^－1·d^－1)
Bauer等^[61]	TPC(50 mg/kg)	他克莫司(剂量未说明)		最长存活50
	Ati－CD2b(1～4 mg/kg)	西罗莫司(剂量未说明)
		MMF(25～110 mg/kg)
		甲泼尼龙(逐渐减量，剂量未说明)
Mcgregor等^[41]	TPC(50 mg/kg)	他克莫司(血药浓度维持在20～30 ng/mL)		96(15，37)
	利妥昔单抗(19 mg/kg，每周)	西罗莫司(血药浓度维持在20～30 ng/mL)
	甲泼尼龙(逐渐减量，剂量未说明)
Mohiuddin等^[27]	ATG(5 mg/kg)	抗CD40单抗(10～50 mg/kg)/抗CD40单抗(20～50 mg/kg)	EPO(200 U/kg)	70(21，236)
	利妥昔单抗(19 mg/kg，每周)	MMF(20 mg/kg，2次/d)	肝素(50～400 U/h)
	眼镜蛇毒因子(6 mg/d)	甲泼尼龙(逐渐减量，剂量未说明)	更昔洛韦(5 mg·kg^－1·d^－1)
			头孢唑林钠(250 mg/kg，2次/d，共7 d)
Mohiuddin等^[33]	ATG(5 mg/kg)	抗CD40(10～50 mg/kg)	EPO(200 U/kg)	298(159，945)
	抗CD20b单抗(19 mg/kg)	阿司匹林(81 mg)	肝素(50～400 U/h)
	抗CD40b单抗(50 mg/kg)	MMF(20 mg/kg)	更昔洛韦(5 mg·kg^－1·d^－1)
		甲泼尼龙(2 mg/kg，逐渐减量)	头孢唑林钠(250 mg/kg，2次/d，共7 d)
Längin等^[2]	ATG(5 mg/kg)	抗CD40(50 mg/kg)	低分子肝素(20～40 U·kg^－1·h^－1)	195(159，945)
	抗CD2b(19 mg/kg)	MMF(40 mg/kg)	EPO[2 000 U(移植前第7天及移植当天各应用1次)]
	抗CD40b(50 mg/kg)	甲泼尼龙(10 mg/kg，逐渐减量)	更昔洛韦(5 mg·kg^－1·d^－1)
		雷帕霉素(血药浓度维持在5～10 ng/mL)	头孢唑林钠(250 mg/kg，2次/d，共7 d)

文献	免疫诱导方案	免疫抑制维持方案	其它支持治疗方案	受体存活情况(d)
Kuuaki等^[47]	ATG(50 mg/kg)	抗人CD154单抗(25 mg/kg)	阿司匹林[40 mg(隔日)]	最长存活78
	LoCD2b(1～4 mg/kg)	抗CD40单抗(20～25 mg/kg)	肝素(5～60 U·kg^－1·h^－1)
	胸腺照射(700 cGy)	MMF(25～110 mg/kg)	更昔洛韦(5 mg·kg^－1·d^－1)
	眼镜蛇毒因子(6 mg/d)	甲泼尼龙(4.0～0.5 mg/kg)	左氧氟沙星(10 mg·kg^－1·d^－1)
Bauer等^[61]	TPC(50 mg/kg)	他克莫司(剂量未说明)		最长存活50
	Ati－CD2b(1～4 mg/kg)	西罗莫司(剂量未说明)
		MMF(25～110 mg/kg)
		甲泼尼龙(逐渐减量，剂量未说明)
Mcgregor等^[41]	TPC(50 mg/kg)	他克莫司(血药浓度维持在20～30 ng/mL)		96(15，37)
	利妥昔单抗(19 mg/kg，每周)	西罗莫司(血药浓度维持在20～30 ng/mL)
	甲泼尼龙(逐渐减量，剂量未说明)
Mohiuddin等^[27]	ATG(5 mg/kg)	抗CD40单抗(10～50 mg/kg)/抗CD40单抗(20～50 mg/kg)	EPO(200 U/kg)	70(21，236)
	利妥昔单抗(19 mg/kg，每周)	MMF(20 mg/kg，2次/d)	肝素(50～400 U/h)
	眼镜蛇毒因子(6 mg/d)	甲泼尼龙(逐渐减量，剂量未说明)	更昔洛韦(5 mg·kg^－1·d^－1)
			头孢唑林钠(250 mg/kg，2次/d，共7 d)
Mohiuddin等^[33]	ATG(5 mg/kg)	抗CD40(10～50 mg/kg)	EPO(200 U/kg)	298(159，945)
	抗CD20b单抗(19 mg/kg)	阿司匹林(81 mg)	肝素(50～400 U/h)
	抗CD40b单抗(50 mg/kg)	MMF(20 mg/kg)	更昔洛韦(5 mg·kg^－1·d^－1)
		甲泼尼龙(2 mg/kg，逐渐减量)	头孢唑林钠(250 mg/kg，2次/d，共7 d)
Längin等^[2]	ATG(5 mg/kg)	抗CD40(50 mg/kg)	低分子肝素(20～40 U·kg^－1·h^－1)	195(159，945)
	抗CD2b(19 mg/kg)	MMF(40 mg/kg)	EPO[2 000 U(移植前第7天及移植当天各应用1次)]
	抗CD40b(50 mg/kg)	甲泼尼龙(10 mg/kg，逐渐减量)	更昔洛韦(5 mg·kg^－1·d^－1)
		雷帕霉素(血药浓度维持在5～10 ng/mL)	头孢唑林钠(250 mg/kg，2次/d，共7 d)

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