首页|基于胚胎补偿技术在猪体内再造人源中肾

基于胚胎补偿技术在猪体内再造人源中肾

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肾脏移植是针对终末期肾脏疾病的首选治疗手段.但供体肾源短缺严重限制了这一有效疗法的临床应用.基于胚胎补偿技术的器官异种体内再造策略已被视为解决器官短缺问题的理想方案.然而,能否借助该策略在大动物体内获得可用于移植的人源肾脏尚未可知.本研究首先向人诱导多能干细胞中转入促增殖基因MYCN及抗凋亡基因BCL2,随后利用先前开发的可用于高效获取人类早期胚胎样干细胞的培养体系4CL对其培养,获得了可用于进行异种胚胎嵌合的理想人源供体细胞,并针对该细胞的特性,对胚胎补偿技术体系进行了全方位优化.同时,该研究成功构建了中肾缺陷、后肾完全缺失的新型肾脏缺陷猪模型.依赖于上述研究基础,本研究首次在异种大动物猪体内实现了人源中肾再造.经检测,嵌合中肾内的人源细胞占比高达70％,其参与构成的中肾小管占比可达58％.更为重要的是,这些细胞会表达与肾脏发育相关的重要功能性基因,表明其能够分化成为具有肾脏发育功能的细胞类型,具有支持后肾形成的潜能.该项研究是世界范围内首次成功实现的人源功能性实质器官异种体内再造,为解决供体器官严重短缺问题开辟新方向.
Generation of a Humanized Mesonephros in Pigs via Embryo Complementation
Organ transplantation is the best way for treating end-stage kidney diseases,but is limited by the shortage of donor organs.Generating human organs in large mammals through embryo complementation holds great potential to solve it.However,it remains unknown whether it is feasible to grow human kidneys in large mammals through this approach.In this study,hiPSCs were transferred with proliferation-promoting gene MYCN and the anti-apoptotic gene BCL2 to enhance the competitiveness and survival ability of cells in pig embryos,and then were induced into naive state with a special medium(4CL),created an ideal donor cell type for chimeric in-tegration.Besides,the embryo complementation technique was comprehensively optimized and a novel pig model with partial mesonephric-deficient and complete metanephros deficiency was generated.Based on above efforts,human mesonephros kidneys were grown inside nephric-deficient pigs.The proportion of human-derived cells in the chimeric mesonephros reached up to 70％,and the proportion of the mesonephric tubules reach a maximum of 58％.Importantly,these cells expressed functional markers for kidney development,indicating that human donor cells could differentiate into functional cells and hold potential for the formation of metanephros.For the first time,this study validates the feasibility of generating a humanized solid organ in organogenesis-disabled pigs,opening a new avenue to solve the shortage of human organs for transplantation.

embryo complementation technologyxenogeneic organogenesishuman pluripotent stem cellsnephric-defective pig model

王教伟、栗楠、戴祯、赖良学

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中国科学院再生生物学重点实验室,广东省干细胞与再生医学重点实验室,中国科学院广州生物医药与健康研究院,中国科学院大学,广州 510530

胚胎补偿技术 器官异种再造 人多能干细胞 肾脏缺陷猪模型

中国科学院战略先导项目中国科学院战略先导项目中国科学院战略先导项目国家重点研发计划国家重点研发计划国家重点研发计划

XDA16030503XDA16030502XDA160305042022YFF07106012022YFA11054032022YFA1105404

2024

10.11844/cjcb.2024.02.0001

中国细胞生物学学报
中国科学院上海生命科学研究院,生物化学与细胞生物学研究所,中国细胞生物学学会

中国细胞生物学学报

CSTPCD
影响因子：0.554
ISSN：1674-7666
年,卷(期)：2024.46(2)
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