每经记者｜林姿辰 每经编辑｜张海妮 陈忠华： "异种移植研究的唯一动力是器官短缺。" "在器官捐献初级阶段，我们面临的主要挑战是建立法治框架下的器官捐献体系和倡导公民逝世后自愿无偿器官捐献。" "在不远的将来，产业化医用器官，包括异种器官和人工器官，必将成为除人体捐献器官以外的源源不断的补充性来源。我满怀信心地迎接这个新时代的到 来。" 移植猪器官后"会不会变成猪"？不可能！ 种牛痘是英国医生爱德华·琴纳于18世纪末发明的天花预防方法，通过接种牛痘病毒使人体获得对天花的免疫力。当时很多人怀疑接种了牛痘以后是不是会 变成牛。于是漫画家就非常生动形象地画出了当时人们的担忧：身上长出牛头、牛角之类的特征。 图片来源：受访者提供 猪器官在活体人体内存活时间最长的案例已诞生。 当地时间9月8日，据《自然》新闻（Nature News）报道，67岁的美国男子蒂姆·安德鲁斯（Tim Andrews）在接受基因编辑猪肾脏移植后，已存活接近8个 月。就在两周前，中国研究团队刚在国际学术期刊《自然·医学》（Nature Medicine）在线发表论文，报告了世界首例将基因编辑猪肺移植到脑死亡人体内的 成功案例。 陈忠华是论文的共 ...

Core Points - The case of Tim Andrews, a 67-year-old American man, marks a significant milestone in xenotransplantation, as he has survived nearly 8 months after receiving a genetically edited pig kidney transplant, the longest survival time recorded for such a procedure [1][3][4] - The transplant was performed by Dr. Tatsuo Kawai at Massachusetts General Hospital, who believes that pig kidney transplants could become routine surgeries within five years, despite existing challenges [1][5] Group 1: Patient and Procedure Details - Tim Andrews is the fourth patient in the U.S. to receive a genetically edited pig kidney transplant, having been diagnosed with end-stage kidney disease and requiring dialysis for over two years prior to the surgery [3][4] - The pig kidney used in the transplant underwent 69 genomic edits, including 59 to inactivate porcine endogenous retroviruses (PERV) and 10 to eliminate three types of glycan antigens to prevent hyperacute rejection [3][4] - The transplant has allowed Andrews to stop dialysis, and he is currently on a unique immunosuppressive treatment plan [4][8] Group 2: Research and Future Prospects - The FDA has approved eGenesis to conduct trials involving genetically edited pig kidney transplants in 33 patients aged 50 and above with end-stage kidney disease [1][3] - Dr. Kawai emphasizes the importance of the first six months post-transplant for both patient and organ survival, noting that managing fluid balance and immunosuppressive drug dosages is more complex than in human-to-human transplants [7][8] - The success of Andrews and another patient, Bill Stewart, who has survived three months post-transplant, indicates significant advancements in xenotransplantation technology [4][8] Group 3: Historical Context and Challenges - Historical attempts at xenotransplantation faced severe immune rejection, with survival times ranging from minutes to days in earlier cases involving primate organs [10] - The field of organ transplantation has seen a dramatic increase in success rates over the past four decades, from less than 50% to over 95% for human-to-human transplants [10] - Future breakthroughs in xenotransplantation may include heart transplants, although challenges remain due to the critical condition of patients and the complexity of translating these techniques to clinical applications [10]

Core Viewpoint - The successful transplantation of genetically edited pig kidneys into humans marks a significant milestone in xenotransplantation, with the longest survival time recorded at nearly 8 months for patient Tim Andrews [1][2]. Group 1: Patient and Procedure Details - Tim Andrews, a 67-year-old man, received a genetically edited pig kidney transplant after suffering from end-stage renal disease and being on dialysis for over two years [2][3]. - The transplant involved a pig kidney with 69 genomic edits, including 59 to inactivate porcine endogenous retroviruses (PERV) and 10 to eliminate three types of glycan antigens to prevent hyperacute rejection [2][3]. - The surgery was performed by Dr. Tatsuo Kawai, who believes that pig kidney transplants could become routine within five years despite existing challenges [1][4]. Group 2: Research and Regulatory Aspects - The FDA has approved eGenesis to conduct trials involving genetically edited pig kidney transplants in 33 patients aged 50 and above with end-stage renal disease [1][2]. - The ongoing research aims to identify the optimal combination of gene edits necessary for successful xenotransplantation, as the specific human proteins critical for success remain under debate [3][4]. Group 3: Historical Context and Future Prospects - Historically, the survival times for patients receiving animal organ transplants ranged from 4 minutes to 70 days, highlighting the advancements made in xenotransplantation technology [3][5]. - The next potential breakthrough in xenotransplantation may involve heart transplants, although challenges remain due to the critical condition of patients and the complexity of the procedure [6][7].

Core Viewpoint - The article discusses the successful transplantation of genetically edited pig lungs into a brain-dead human, marking a significant advancement in xenotransplantation, which aims to address the global organ shortage crisis [1][5][18]. Group 1: Background and Importance of Xenotransplantation - Approximately 2 million people worldwide require organ transplants each year, but only about 10% receive suitable organs, highlighting the critical shortage of transplantable organs [5]. - Xenotransplantation, particularly using pig organs, is considered a promising solution to the organ shortage problem [5][9]. Group 2: Research and Development - The research team led by Professor He Jianxing from Guangzhou Medical University successfully transplanted a genetically edited Bama pig's left lung into a brain-dead patient, maintaining ventilation and gas exchange for 9 days [5][18]. - Since 2021, several cases of pig-to-human organ transplants have been reported globally, involving various organs such as hearts, kidneys, and livers [7]. Group 3: Advantages of Using Pigs - Pigs are preferred over primates for organ donation due to their abundant resources, smaller size, high survival rates, and genetic stability, along with significant anatomical and physiological similarities to humans [9][10]. - The evolutionary distance between pigs and humans reduces the risk of zoonotic diseases and ethical concerns associated with using primates [9]. Group 4: Challenges in Xenotransplantation - Despite the advantages, xenotransplantation faces challenges such as cross-species rejection and the risk of infections, which have historically hindered research progress [10][18]. - Recent advancements in gene editing technologies, such as CRISPR/Cas9, have enabled the development of genetically modified pigs that minimize immune rejection and viral infection risks [10][12]. Group 5: Clinical Trials and Future Prospects - Currently, xenotransplantation trials are primarily conducted in China and the United States, with significant milestones achieved in heart and kidney transplants [14][16]. - The recent lung transplant case represents a critical step towards clinical applications, although experts emphasize the need for cautious progression through further trials and research [18][19].

Core Insights - The research team from Guangzhou Medical University successfully transplanted a gene-edited pig lung into a human, marking a significant milestone in xenotransplantation [1][3][4] - The transplanted lung functioned for 9 days, demonstrating the potential of gene-edited organs to address the shortage of human organ donors [1][6][9] Group 1: Research Achievements - The pig lung was genetically modified using CRISPR technology to reduce immune rejection risks by silencing three genes and adding three human protein genes [9][11] - The patient, a 39-year-old brain-dead man, showed no immediate acute rejection of the pig lung, which is a common issue in organ transplants [4][11] - The study highlights the potential for gene-edited pig organs to be more compatible with human physiology, which could alleviate the organ donor shortage [3][6] Group 2: Clinical Observations - The transplanted lung maintained its function for 216 hours, with no signs of hyperacute rejection during the monitoring period [13][15] - Despite some immune response and organ damage observed, the lung was able to perform gas exchange effectively for the duration of the experiment [4][8][11] - The research team plans to optimize gene editing strategies and anti-rejection treatments to extend the survival and functionality of transplanted organs [8][15] Group 3: Future Directions - The study is seen as a step forward in the challenging field of xenotransplantation, with further research needed to address the challenges of organ rejection and infection [14][15] - Experts emphasize the importance of ethical considerations and safety protocols in conducting such high-risk research [15] - The research team aims to apply their findings to clinical settings, potentially transforming the landscape of organ transplantation [8][14]

Core Viewpoint - The successful transplantation of gene-edited pig lungs into a human marks a significant milestone in xenotransplantation, potentially addressing the shortage of human organ donors [1][5][12]. Group 1: Research Achievement - A team led by Professor He Jianxing from Guangzhou Medical University successfully transplanted a gene-edited left lung from a Bama pig into a brain-dead patient, with the lung functioning for 9 days [1][12]. - The research was published on August 25 in the journal Nature Medicine, receiving high praise from international experts as a milestone in the field [2][4]. Group 2: Implications for Organ Transplantation - This achievement highlights the potential of gene-edited pig organs to be more compatible with human biology, which could alleviate the shortage of lung transplant donors [5][9]. - The global demand for organ transplants is increasing, and xenotransplantation is seen as a promising solution to the donor shortage crisis [9]. Group 3: Technical Details - The transplanted pig lung underwent six CRISPR gene edits to silence three genes that trigger immune responses and to introduce three human protein genes to reduce immune risks [14]. - Despite some immune response and organ damage observed, there was no immediate strong rejection of the gene-edited pig lung [6][17]. Group 4: Future Directions - The research team plans to optimize gene editing strategies and anti-rejection treatments to extend the survival and functionality of transplanted organs [13][26]. - Further studies are needed to address challenges related to organ rejection and infection before this procedure can be translated into clinical practice [26].

Core Viewpoint - The research team from China has successfully performed the world's first gene-edited pig lung transplant into a brain-dead human, marking a significant milestone in the field of xenotransplantation and potentially addressing the shortage of organ donors [3][4]. Group 1: Research Details - The transplant involved a left lung from a genetically edited Bama pig, which underwent six gene edits to reduce immune rejection risks [3]. - Post-surgery monitoring indicated that the transplanted lung maintained ventilation and gas exchange functions for nine days without acute rejection or active infection [3][4]. - The research was conducted under strict adherence to national laws and ethical guidelines, with the brain-dead subject's family consenting to the study [4]. Group 2: Expert Opinions - International experts have praised the achievement, highlighting the challenges of lung transplantation compared to other organs due to the delicate physiological balance and exposure to external air [5]. - The director of Spain's National Transplant Organization described the Chinese team's work as a milestone in the field of xenotransplantation [5]. Group 3: Future Directions - The research team plans to optimize gene editing strategies and anti-rejection treatments to extend the survival and functionality of transplanted organs [3]. - There are intentions to apply a self-developed non-invasive technique in future xenotransplantation trials to minimize damage to the donor lung [3].

Core Viewpoint - The research team from China has successfully performed the world's first gene-edited pig lung transplant into a brain-dead human, marking a significant milestone in the field of xenotransplantation and addressing the shortage of organ donors [1][2]. Group 1: Research Details - The study involved the transplantation of a left lung from a genetically edited Bama pig into a brain-dead individual, simulating a common clinical single-lung transplant procedure [1]. - The donor pig underwent six genetic modifications to reduce the risk of immune rejection after the organ was transplanted into a human [1]. - Post-surgery monitoring indicated that the transplanted lung maintained ventilation and gas exchange functions for nine days without acute rejection, and no active infection was detected during this period [1]. Group 2: Implications and Future Directions - The increasing global demand for organ transplants has led to xenotransplantation being viewed as a potential solution to the donor shortage crisis [1]. - The research team plans to further optimize gene editing strategies and anti-rejection treatment protocols to extend the survival and functionality of transplanted organs [1]. - The team aims to apply their independently developed non-invasive technology in future xenotransplantation trials to minimize mechanical ventilation damage to the donor lung, facilitating the transition of xenotransplantation to clinical applications [1]. Group 3: Ethical Considerations - The research adhered to national laws, regulations, and ethical guidelines, receiving approval from the hospital's ethics committee and other oversight bodies [2]. - The brain-dead subject's family consented to participate in the study to support medical advancement, and the study was concluded at the family's request on the ninth day [2]. Group 4: Expert Opinions - International experts have praised the research, noting that previous xenotransplantation trials were limited to kidneys, hearts, and livers, with lung transplantation presenting unique challenges due to its physiological balance and exposure to external air [2]. - The director of Spain's National Transplant Organization highlighted the achievement as a milestone in the field of xenotransplantation [2].

Group 1 - The event in Zizhong, Sichuan, highlighted significant advancements in xenotransplantation, achieving breakthroughs in both clinical and preclinical trials, and setting new survival records in Asia for xenotransplantation [1][3] - The first case of pig kidney transplantation in Asia and the fifth globally has reached 105 days post-operation, establishing a new record in the region [3] - Preclinical trials involving pig kidney transplants to monkeys have surpassed 233 days of survival, breaking the previous Asian record of 221 days held by South Korea [3][4] Group 2 - Zizhong County has prioritized xenotransplantation as a key project to capture the high ground in the biomedicine industry, leading to significant breakthroughs in gene pig breeding and preclinical trials since 2019 [4][5] - The event facilitated partnerships between Zhongke Aoge Biotechnology Co., Ltd. and various medical institutions, injecting new vitality into clinical trials and the translation of xenotransplantation results [7] - The company aims to revolutionize the organ transplant landscape by developing not only kidney transplants but also skin and red blood cell treatments, with the goal of making xenotransplantation a routine medical practice within 5-10 years [7]