Supercooled kidneys have been transplanted into pigs in a “landmark achievement”
Supercooled kidneys have been transplanted into pigs in a “landmark achievement”
过冷肾脏成功移植入猪体内，被誉为“里程碑式成就”
EXECUTIVE SUMMARY When it comes to organ donation, time is everything. As soon as an organ has been carefully removed from a donor’s body, it starts to deteriorate. Surgeons have a matter of hours to get it into a recipient. Leave it too long and the organ will become unusable. In most cases, organs will be kept on ice during that time, at around 4 °C (39 °F). They cannot be frozen—in previous attempts, ice has formed, causing all kinds of damage. Matthew Powell Palm at Texas A&M University and his colleagues have an alternative solution—a device that allows organs to be cooled to -4 °C (25 °F) without forming any ice. Now, in new research with pig organs, his team has shown that kidneys, at least, can be supercooled and preserved in the device for days. Once rewarmed, the organs have been successfully transplanted into animals, and they seem to do better than organs kept on ice. The work represents “a landmark achievement,” says Kevin Myer, president and CEO of LifeGift, an organ procurement organization based in Texas, who was not involved in the research.
执行摘要 在器官捐献领域，时间就是一切。一旦器官从捐献者体内被小心取出，它就开始退化。外科医生只有几个小时的时间将其移植给受体。如果时间过长，器官就会变得无法使用。在大多数情况下，器官在此期间会被保存在约 4 °C (39 °F) 的冰上。它们不能被冷冻——在以往的尝试中，冰晶的形成会造成各种损害。德克萨斯农工大学的 Matthew Powell Palm 及其同事提出了一种替代方案——一种可以将器官冷却至 -4 °C (25 °F) 而不形成冰晶的装置。现在，在针对猪器官的最新研究中，他的团队证明了至少肾脏可以通过该装置进行过冷保存，且能维持数天。复温后，这些器官被成功移植到动物体内，其表现似乎优于冰上保存的器官。未参与此项研究的德克萨斯州器官获取组织 LifeGift 的总裁兼首席执行官 Kevin Myer 表示，这项工作代表了“一个里程碑式的成就”。
Cooling organs Powell Palm hopes this approach could ultimately help ease the organ shortage crisis. Today, there are more than 104,000 people waiting for a kidney transplant in the US alone. It is estimated that 17 people die every day in the US while waiting for a transplant. That’s partly due to a lack of donated kidneys, but it’s also because many of those that are available never make it to a recipient. In some years, around one in three donated kidneys end up being discarded, often because they end up too degraded to use by the time they reach a recipient. Kidneys can be stored on ice for around 24 hours or placed in devices that aim to mimic the conditions of the body, also for up to around 24 hours. That’s not always long enough to find a suitable recipient and transport the organ, says Myer.
冷却器官 Powell Palm 希望这种方法最终能有助于缓解器官短缺危机。如今，仅在美国就有超过 104,000 人在等待肾脏移植。据估计，美国每天有 17 人在等待移植的过程中死亡。这部分是因为捐献肾脏的短缺，但也因为许多可用的肾脏最终未能到达受体手中。在某些年份，约有三分之一的捐献肾脏最终被丢弃，通常是因为它们在到达受体时已经退化到无法使用。肾脏可以在冰上保存约 24 小时，或放置在旨在模拟人体环境的装置中，同样最多只能保存约 24 小时。Myer 表示，这往往不足以找到合适的受体并完成器官运输。
Scientists around the world have been working on ways to store organs for longer by cooling them to even chillier temperatures. Cooling an organ slows its metabolism—the colder you go, the greater the effect, and the longer you can store it. We’ve long been able to successfully cryopreserve eggs, sperm, and embryos, but it’s much harder to freeze large organs. Teams have been exploring various temperatures and cryoprotectants (chemicals that essentially work like antifreeze), but so far no one has been able to freeze human organs for transplantation. As a thermodynamicist, Powell Palm explored another approach. By keeping an organ submerged at a constant pressure, it should be possible to prevent the formation of ice at temperatures a little below 0 °C, without the need for cryoprotectants (which might have side effects and would need to be approved before being used in human transplants).
世界各地的科学家一直致力于通过将器官冷却到更低的温度来延长其保存时间。冷却器官可以减缓其新陈代谢——温度越低，效果越显著，保存时间也就越长。我们长期以来已经能够成功冷冻保存卵子、精子和胚胎，但冷冻大型器官要困难得多。各研究团队一直在探索各种温度和冷冻保护剂（本质上像防冻剂一样的化学物质），但到目前为止，还没有人能够冷冻用于移植的人体器官。作为一名热力学家，Powell Palm 探索了另一种方法。通过在恒定压力下将器官浸没，理论上可以在略低于 0 °C 的温度下防止冰晶形成，而无需使用冷冻保护剂（冷冻保护剂可能具有副作用，且在用于人体移植前需要经过审批）。
To test this theory, Powell Palm and his colleagues have created a device that does just that. The device itself is essentially a hermetically sealed chamber with a transparent lid. At its base is a device that monitors the organ’s temperature and checks for the formation of ice. Organs are submerged in a solution that is already commonly used to preserve them for transplant. “I always describe this as low-tech high science,” says Powell Palm. “A lot of work has gone into understanding the … kinetics at play in this system, but ultimately … it’s quite simple.”
为了验证这一理论，Powell Palm 及其同事制造了一种能够实现这一目标的装置。该装置本质上是一个带有透明盖子的密封腔室。其底部设有一个监测器官温度并检查是否形成冰晶的装置。器官被浸没在一种通常用于移植保存的溶液中。“我总是将其描述为低技术含量的高端科学，”Powell Palm 说，“为了理解该系统中的动力学原理，我们投入了大量工作，但归根结底……它非常简单。”
Supercooled kidneys To test their device, Powell Palm and his colleagues first removed single kidneys from pigs. The organs were flushed with the same commonly used solution to remove the blood, just as transplant organs are. The team then kept some kidneys on ice for either two hours or 24 hours, to mimic standard conditions used in human transplantation. They also put some of the removed kidneys in their device for 24, 48, or 72 hours. The stored kidneys were then each transplanted back into the original donor pigs. Each pig’s second kidney was removed in the same procedure, leaving each animal with only the kidney that had been stored, and reimplanted.
过冷肾脏 为了测试他们的装置，Powell Palm 及其同事首先从猪身上摘除了单侧肾脏。这些器官像移植器官一样，用同样的常用溶液冲洗以去除血液。随后，研究团队将部分肾脏在冰上保存 2 小时或 24 小时，以模拟人体移植中的标准条件。他们还将部分摘除的肾脏放入他们的装置中保存 24、48 或 72 小时。随后，这些保存后的肾脏被分别移植回原来的供体猪体内。每头猪的另一侧肾脏在手术中被摘除，使每只动物体内仅保留那个经过保存并重新植入的肾脏。
Once the 24-hour supercooled kidneys were transplanted, they immediately began producing urine—a key indication that they were working. The team members also measured other markers of kidney function and found that the organs appeared to be working normally within about 10 days of being transplanted. That’s slower than kidneys stored on ice for two hours but much quicker than kidneys kept on ice for 24 hours, says Powell Palm. The organs that were kept supercooled for 48 and 72 hours performed similarly, he says. “Even at three days—triple the clinical standard—we’re getting recovery that is faster than … [what has been] the gold standard for the last three decades,” he says. “So we’re really, really pumped about this.”
当 24 小时过冷肾脏被移植后，它们立即开始产生尿液——这是器官功能正常的关键指标。团队成员还测量了其他肾功能指标，发现这些器官在移植后约 10 天内似乎已恢复正常工作。Powell Palm 表示，这比在冰上保存 2 小时的肾脏恢复得慢，但比在冰上保存 24 小时的肾脏要快得多。他说，过冷保存 48 小时和 72 小时的器官表现相似。“即使在三天后——是临床标准的三倍——我们获得的恢复速度也比过去三十年的黄金标准要快，”他说，“所以我们对此感到非常非常兴奋。”
“It is impressive,” says Heidi Yeh, a transplant surgeon at Mass General Brigham for Children, who also researches organ preservation technologies. “Often kidneys that have been stored for 48 hours [in other studies] take a week or two before they start working again.”
“这令人印象深刻，”麻省总医院布里格姆儿童医院的移植外科医生 Heidi Yeh 说道，她同时也研究器官保存技术，“通常（在其他研究中）保存 48 小时的肾脏需要一两周时间才能恢复工作。”
Organs that grow The supercooled organs seem to work well in the long term, too. Over a 30-day period, the pigs grew by around 30%—and the kidneys grew with them, almost doubling in size to compensate for both the pigs’ growth and the lack of a second kidney. The team monitored one of the pigs for 200 days before removing and analyzing its kidney. Even at that point the organ looked healthy, says Powell Palm. He and his colleagues presented the findings at the American Transplant Congress in Boston last month. Earlier this year, researchers in Canada showed they could also cool pig kidneys to below-zero temperatures and transplant them into pigs. The team’s protocol included the use of a cryoprotectant, and organs were stored for up to 48 hours before being transplanted into pigs. Those organs survived for a week.
生长的器官 过冷保存的器官在长期表现上也很好。在 30 天的时间里，猪的体重增长了约 30%——肾脏也随之生长，体积几乎翻了一番，以补偿猪的生长和缺失的另一侧肾脏。团队对其中一头猪进行了 200 天的监测，随后摘除并分析了其肾脏。Powell Palm 说，即使在那时，该器官看起来依然健康。他和同事在上个月于波士顿举行的美国移植大会上展示了这些发现。今年早些时候，加拿大研究人员也证明了他们可以将猪肾冷却到零下温度并移植到猪体内。该团队的方案包括使用冷冻保护剂，器官在移植到猪体内前最多保存了 48 小时。那些器官存活了一周。