本文为原文前 6,000 字符的节选翻译，完整内容请查看原文。

Pig kidneys that were “frozen” for a year have been brought back to life

EXECUTIVE SUMMARY Pig kidneys that were cooled to -150 °C and stored in a freezer for months have been successfully rewarmed and shown to work again for the first time, say scientists. They hope to replicate the findings with human organs. The kidneys—which are similar in size to human ones—were left in a glass-like state, in one case for over a year. Once they had been rewarmed, tested in machines, and transplanted into pigs, the kidneys regained their color and made urine—key signs they were working.

执行摘要：科学家表示，猪肾脏在冷却至 -150°C 并冷冻储存数月后，首次被成功复温并证明可以再次发挥功能。他们希望在人体器官上复制这一研究结果。这些肾脏的大小与人类肾脏相似，它们被置于一种玻璃化状态，其中一个样本被保存了超过一年。在经过复温、机器测试并移植到猪体内后，这些肾脏恢复了色泽并开始产生尿液——这是它们正常工作的关键迹象。

“Ten years ago … I wouldn’t say I had high hopes it was actually going to work,” says Erik Finger, a transplant surgeon at the University of Minnesota who co-led the work. “After we did the last transplant, I walked out of the room and said, ‘This is a big deal.’” The research was shared at the preprint server bioRxiv and has not yet been peer-reviewed. The kidneys aren’t perfect, and the researchers have yet to demonstrate that they can sustain life over the long term. But the results represent a milestone achievement, say others in the field.

明尼苏达大学的移植外科医生、该研究的共同负责人埃里克·芬格（Erik Finger）表示：“十年前……我不敢说我对此抱有很大希望。在我们完成最后一次移植手术后，我走出房间说：‘这是一件大事。’”这项研究已在预印本服务器 bioRxiv 上发布，尚未经过同行评审。这些肾脏并不完美，研究人员也尚未证明它们能够长期维持生命。但该领域的其他专家认为，这些结果代表了一项里程碑式的成就。

“Thank God that someone’s actually managed to do it in one organ and prove that it works,” says Peter Kilbride, a cryobiologist and cofounder of Kyros Kairos, a company focused on improving funding for cryopreservation research, who was not involved in the research. “For years, people have been trying and failing to get to this step. Finally, we’ve got this breakthrough.” “Their work is amazing and will enable us to truly, indefinitely bank organs,” says Korkut Uygun, a biomedical engineer and professor of surgery at Harvard Medical School, who was also not involved in the research. “It is a revolutionary time for transplantation.”

未参与该研究的低温生物学家、专注于改善低温保存研究资金的 Kyros Kairos 公司联合创始人彼得·基尔布莱德（Peter Kilbride）表示：“感谢上帝，终于有人成功在一个器官上做到了这一点，并证明了它是有效的。多年来，人们一直试图达到这一步却屡屡失败。我们终于取得了这一突破。”同样未参与该研究的哈佛医学院生物医学工程师兼外科教授科尔库特·乌贡（Korkut Uygun）表示：“他们的工作令人惊叹，将使我们能够真正实现器官的无限期储存。这是移植领域革命性的时刻。”

Buying time Every year, tens of thousands of organ transplants take place in the US alone. These procedures are thought to have saved 2 million years of life in the last 25 years. But there’s plenty of room for improvement. One major challenge is the lack of available organs. Even when an organ becomes available, it can be difficult to get it to the right recipient within 24 to 36 hours, which is the current limit for preserving human organs. People who receive organ transplants must also take drugs that suppress their immune systems for the rest of their lives. These drugs are meant to stop their bodies from rejecting the new organs. But they come with side effects and increase the risk of infections and cancer.

争取时间：仅在美国，每年就进行数万例器官移植手术。据估计，这些手术在过去 25 年里挽救了 200 万年的生命。但仍有很大的改进空间。一个主要的挑战是缺乏可用的器官。即使有器官可用，也很难在 24 到 36 小时内将其送达合适的受体手中，而这正是目前人类器官保存的极限。接受器官移植的人还必须终身服用抑制免疫系统的药物。这些药物旨在防止身体排斥新器官，但它们会带来副作用，并增加感染和癌症的风险。

The ability to bank organs for long periods of time holds the promise to address all these challenges. Doctors would have more time to match organs to recipients. They’d be able to limit the risk of organ rejection, too—potentially by preparing recipients, and their immune systems, beforehand. “With real organ banking … instead of the patients waiting for the organ, it’s the organs that are waiting for the patients,” says Finger.

长期储存器官的能力有望解决所有这些挑战。医生将有更多时间为受体匹配器官。他们还可以通过提前准备受体及其免疫系统来降低器官排斥的风险。芬格说：“有了真正的器官库……不再是患者等待器官，而是器官在等待患者。”

Scientists have been able to cool cells to ultra-low temperatures through a process called vitrification, which essentially turns them to something like glass. This procedure is already used to store eggs, sperm, and embryos. Vitrifying whole organs is much harder. Some problems can be avoided with cryoprotectants—chemicals that work like antifreeze and prevent damaging ice crystals from forming. But these chemicals tend to be incredibly toxic. It’s also difficult to rapidly and uniformly cool large tissues, and just as hard to evenly rewarm an organ all the way through.

科学家们已经能够通过一种称为“玻璃化”的过程将细胞冷却到超低温，这本质上是将它们变成类似玻璃的状态。该程序已用于储存卵子、精子和胚胎。玻璃化整个器官要困难得多。一些问题可以通过冷冻保护剂来避免——这些化学物质像防冻剂一样，可以防止破坏性的冰晶形成。但这些化学物质往往具有极强的毒性。此外，快速且均匀地冷却大型组织非常困难，而均匀地对整个器官进行复温也同样艰难。

Working with John Bischof, a bioengineer at the University of Minnesota, Finger and colleagues have come up with a solution. Once an organ has been loaded with a cryoprotectant, they infuse it with iron oxide nanoparticles. These nanoparticles don’t do anything to the cells. But when it’s time to rewarm the organ, they can be activated with an electromagnetic field. When the radiofrequency of that field switches between two states, the particles also flip, realigning themselves with the field. That causes them to release heat throughout the organ. Adjusting the power of the field allows the team to control the rate of heating so that it gets faster once the organ reaches -120°C.

芬格与明尼苏达大学的生物工程师约翰·比绍夫（John Bischof）合作，提出了一种解决方案。一旦器官被注入冷冻保护剂，他们就会向其中注入氧化铁纳米颗粒。这些纳米颗粒对细胞没有任何影响。但当需要复温器官时，它们可以通过电磁场激活。当电磁场的射频在两种状态之间切换时，颗粒也会翻转，并与磁场重新对齐。这会导致它们在整个器官中释放热量。调节磁场的功率使团队能够控制加热速率，从而在器官达到 -120°C 后加快加热速度。

The researchers successfully vitrified rat kidneys using this approach in work published in 2023. Back then, they were able to rewarm kidneys that had been kept in a freezer for up to 100 days before transplanting them into rats. Since then, the team has been trying to achieve the same success with bigger organs. Pig kidneys are thought to be a good model for human ones—they’re about the same size and look similar. Rat kidneys weigh around one gram; pig kidneys are around 100. It hasn’t been easy. The cryoprotectant used for vitrifying rat kidneys didn’t work as well in the pig organs. “We had to rediscover and modify the cocktail,” says Bischof. “That’s why it’s taken us three years.”

研究人员在 2023 年发表的一项研究中，利用这种方法成功地对大鼠肾脏进行了玻璃化处理。当时，他们能够将冷冻保存长达 100 天的肾脏复温，并将其移植到大鼠体内。从那时起，该团队一直试图在更大的器官上取得同样的成功。猪肾脏被认为是人类肾脏的良好模型——它们大小相当且外观相似。大鼠肾脏重约一克，而猪肾脏重约 100 克。这并不容易。用于大鼠肾脏玻璃化的冷冻保护剂在猪器官上的效果并不理想。比绍夫说：“我们不得不重新发现并修改这种混合配方。这就是为什么我们花了三年时间。”

Deep-freezing kidneys The first step in the procedure is to remove a kidney from a donor pig. Once it’s out, the kidney is flushed with a commonly used organ preservation solution to remove the blood, bagged, and temporarily laid on a bed of ice in a cooler so it can be taken over to the engineering lab. There, team members unpack the kidney and hook it up to a device they’ve designed to control the organ’s temperature and pressure. Then they start to load it up with the cocktail of cryoprotectants, slowly enough to ensure an even spread through the organ but quickly enough to minimize any toxic effects. It takes around two hours.

深冻肾脏：该过程的第一步是从供体猪身上取出肾脏。取出后，用常用的器官保存液冲洗肾脏以去除血液，装袋并暂时放在冷却器中的冰床上，以便将其带到工程实验室。在那里，团队成员拆开肾脏包装，并将其连接到他们设计的用于控制器官温度和压力的设备上。然后，他们开始注入冷冻保护剂混合液，速度既要慢到足以确保在器官内均匀分布，又要快到足以最大限度地减少任何毒性影响。这大约需要两个小时。

The next step is to infuse the organ with the iron oxide nanoparticles, which are pumped through the organ for around seven to eight minutes, says Finger. Then it’s time to cool the organ by pumping cold nitrogen vapor into a chamber housing it. It’s a delicate process, and the team must ensure that the organ is cooling all the way through. At the same time, they must lower the kidney’s temperature as quickly as possible to prevent ice from forming. “Oftentimes there are multiple people doing different things to make sure that things don’

芬格说，下一步是向器官注入氧化铁纳米颗粒，这些颗粒通过泵送在器官内循环约七到八分钟。接下来是通过向存放器官的腔室泵入冷氮蒸汽来冷却器官。这是一个精细的过程，团队必须确保器官完全冷却。同时，他们必须尽可能快地降低肾脏的温度，以防止冰晶形成。“通常会有多个人同时进行不同的操作，以确保事情不会……”