Stem cells reverse woman’s diabetes — a world first
干细胞逆转女性糖尿病--世界首例

A 25-year-old woman with type 1 diabetes started producing her own insulin less than three months after receiving a transplant of reprogrammed stem cells¹. She is the first person with the disease to be treated using cells that were extracted from her own body.
一名25岁的1型糖尿病妇女在接受重编程干细胞移植后不到三个月，就开始产生自己的胰岛素¹ 。她是第一位使用从自己体内提取的细胞进行治疗的患者。

“I can eat sugar now,” said the woman, who lives in Tianjing, on a call with Nature. It has been more than a year since the transplant, and, she says, “I enjoy eating everything — especially hotpot.” The woman asked to remain anonymous to protect her privacy.
"我现在可以吃糖了，"这位居住在天津的女士在与Nature的通话中说道。移植手术已经一年多了，她说："我什么都喜欢吃，尤其是火锅。为了保护个人隐私，这位女士要求匿名。

James Shapiro, a transplant surgeon and researcher at the University of Alberta in Edmonton, Canada, says the results of the surgery are stunning. “They’ve completely reversed diabetes in the patient, who was requiring substantial amounts of insulin beforehand.”
加拿大埃德蒙顿阿尔伯塔大学的移植外科医生兼研究员詹姆斯-夏皮罗说，手术效果令人惊叹。"他们完全逆转了病人的糖尿病，而病人之前需要大量的胰岛素"。

The study, published in Cell today, follows results from a separate group in Shanghai, China, who reported in April that they had successfully transplanted insulin-producing islets into the liver of a 59-year-old man with type 2 diabetes². The islets were also derived from reprogrammed stem cells taken from the man’s own body and he has since stopped taking insulin.
这项研究发表在今天的《细胞》上。此前，中国上海的另一个研究小组在4月份报告说，他们成功地将产生胰岛素的小胰岛移植到一名59岁2型糖尿病² 患者的肝脏中。这些小胰岛也是从该男子体内提取的重编程干细胞衍生出来的，此后他就不再服用胰岛素了。

The studies are among a handful of pioneering trials using stem cells to treat diabetes, which affects close to half a billion people worldwide. Most of them have type 2 diabetes, in which the body doesn’t produce enough insulin or its ability to use the hormone diminishes. In type 1 diabetes, the immune system attacks islet cells in the pancreas.
这些研究是利用干细胞治疗糖尿病的少数开创性试验之一。他们中的大多数人患有2型糖尿病，即身体不能产生足够的胰岛素，或使用这种激素的能力减弱。在1型糖尿病中，免疫系统会攻击胰腺中的胰岛细胞。

Islet transplants can treat the disease, but there aren’t enough donors to meet the growing demand, and recipients must use immune-suppressing drugs to prevent the body from rejecting the donor tissue.
胰岛移植可以治疗这种疾病，但没有足够的捐赠者来满足日益增长的需求，而且接受者必须使用免疫抑制药物来防止身体排斥捐赠组织。

Stem cells can be used to grow any tissue in the body and can be cultured indefinitely in the laboratory, which means they potentially offer a limitless source of pancreatic tissue. By using tissue made from a person’s own cells, researchers also hope to avoid the need for immunosuppressants.
干细胞可用于培植人体内的任何组织，并可在实验室中无限期培养，这意味着它们有可能提供无限的胰腺组织来源。通过使用由人自身细胞制成的组织，研究人员还希望避免使用免疫抑制剂。

Reprogrammed cells 重编程细胞

In the first trial of its kind, Deng Hongkui, a cell biologist at Peking University in Beijing, and his colleagues extracted cells from three people with type 1 diabetes and reverted them into a pluripotent state, from which they could be moulded into any cell type in the body. This reprogramming technique was first developed by Shinya Yamanaka at Kyoto University in Japan almost two decades ago. But Deng and his colleagues modified the technique³: instead of introducing proteins that trigger gene expression, as Yamanaka had done, they exposed the cells to small molecules. This offered more control over the process.
在首次同类试验中，北京大学细胞生物学家邓宏魁和他的同事们从三名1型糖尿病患者身上提取了细胞，并将它们还原成多能状态，从这种状态出发，它们可以被塑造成人体内的任何细胞类型。近二十年前，日本京都大学的山中伸弥首先开发了这种重编程技术。但邓和他的同事对这项技术进行了修改³ ：他们没有像山中那样引入触发基因表达的蛋白质，而是让细胞接触小分子。这样就能更好地控制这一过程。

The researchers then used the chemically induced pluripotent stem (iPS) cells to generate 3D clusters of islets. They tested the safety and efficacy of the cells in mice and non-human primates.
然后，研究人员利用化学诱导多能干细胞（iPS）生成三维胰岛簇。他们在小鼠和非人灵长类动物身上测试了细胞的安全性和有效性。

In June 2023, in an operation that lasted less than half an hour, they injected the equivalent of roughly 1.5 million islets into the woman’s abdominal muscles — a new site for islet transplants. Most islet transplants are injected into the liver, where the cells cannot be observed. But by placing them in the abdomen, the researchers could monitor the cells using magnetic resonance imaging, and potentially remove them if needed.
2023 年 6 月，在不到半小时的手术中，他们将相当于约 150 万个小胰岛注入这名妇女的腹部肌肉--这是胰岛移植的一个新部位。大多数胰岛移植手术都是将胰岛细胞注入肝脏，因为在肝脏中无法观察到胰岛细胞。但通过将它们放入腹部，研究人员可以利用磁共振成像技术对细胞进行监测，并在必要时将它们取出。

Insulin free 无胰岛素

Two-and-a-half months later, the woman was producing enough insulin to live without needing top-ups, and she has sustained that level of production for more than a year. By that time, the woman had stopped experiencing the dangerous spikes and drops in blood glucose levels, which remained within a target range for more than 98% of the day. “That’s remarkable,” says Daisuke Yabe, a diabetes researcher at Kyoto University. “If this is applicable to other patients, it’s going to be wonderful.”
两个半月后，这名妇女的胰岛素分泌量足以让她在不需要补充胰岛素的情况下生活，而且她已经将这种分泌水平保持了一年多。到那时，这名妇女的血糖水平已经不再出现危险的骤升骤降，一天中超过 98% 的时间都保持在目标范围内。"京都大学糖尿病研究员矢部大辅说："这太了不起了。"如果这适用于其他患者，那将会非常棒"。

The results are intriguing, but they need to be replicated in more people, says Jay Skyler, an endocrinologist at the University of Miami, Florida, who studies type 1 diabetes. Skyler also wants to see that the woman’s cells continue to produce insulin for up to five years, before considering her ‘cured’.
佛罗里达州迈阿密大学研究1型糖尿病的内分泌学家杰伊-斯凯勒（Jay Skyler）说，这些结果令人感兴趣，但需要在更多人身上复制。斯凯勒还希望看到这名妇女的细胞能持续分泌胰岛素长达五年，然后才认为她 "痊愈 "了。

Deng says the results for the other two participants are “also very positive”, and they will reach the one-year mark in November, after which he hopes to expand the trial to another 10 or 20 individuals.
邓说，另外两名参与者的结果 "也非常积极"，他们将在 11 月完成一年的试验，之后他希望将试验扩大到另外 10 或 20 人。

Because the woman was already receiving immunosuppressants for a previous liver transplant, the researchers could not assess whether the iPS cells reduced the risk of rejection of the graft.
由于这名妇女已经因为之前的肝移植接受了免疫抑制剂，研究人员无法评估 iPS 细胞是否降低了移植排斥反应的风险。

Even if the body doesn’t reject the transplant because it doesn’t consider the cells to be ‘foreign’, in people with type 1 diabetes, because they have an autoimmune condition, there is still a risk that the body could attack the islets. Deng says they didn’t see this in the woman because of the immunosuppressants, but they are trying to develop cells that can evade this autoimmune response.
即使身体不会排斥移植，因为它不认为细胞是 "外来的"，但对于1型糖尿病患者来说，由于他们患有自身免疫疾病，身体仍有可能攻击胰岛。邓说，由于使用了免疫抑制剂，他们在这名妇女身上没有发现这种情况，但他们正试图开发出可以逃避这种自身免疫反应的细胞。

Donor cells 捐献细胞

Transplants using the recipient’s own cells have advantages, but the procedures are difficult to scale up and commercialize, say researchers. Several groups have started trials of islet cells created using donor stem cells.
研究人员说，利用受者自身细胞进行移植有其优势，但这种程序难以扩大规模和商业化。一些研究小组已经开始试验使用捐赠者干细胞制造的胰岛细胞。

Preliminary results for one trial, led by Vertex Pharmaceuticals in Boston, Massachusetts, were reported in June. A dozen participants with type 1 diabetes received islets derived from donated embryonic stem cells that were injected into the liver. They were all treated with immunosuppressants. Three months after the transplant, all the participants began producing insulin when glucose was present in their bloodstreams⁴. Some had become insulin independent.
由马萨诸塞州波士顿顶点制药公司（Vertex Pharmaceuticals）领导的一项试验的初步结果于6月公布。十几名1型糖尿病患者接受了从捐赠的胚胎干细胞中提取的小鼠肝脏注射。他们都接受了免疫抑制剂治疗。移植三个月后，当血液中出现葡萄糖时，所有参与者都开始产生胰岛素⁴ 。有些人已经不依赖胰岛素。

Last year, Vertex launched another trial in which islet cells derived from donated stem cells were placed in a device designed to protect them from immune-system attacks. It was transplanted into a person with type 1 diabetes, who did not receive immunosuppressants. “That trial is ongoing,” says Shapiro, who is involved in the study, which aims to enrol 17 individuals.
去年，Vertex公司启动了另一项试验，将从捐赠干细胞中提取的胰岛细胞放入一个装置中，以保护它们免受免疫系统的攻击。它被移植到1型糖尿病患者体内，患者没有接受免疫抑制剂治疗。"夏皮罗说："这项试验正在进行中。

Yabe is also about to start a trial using islet cells produced using donor iPS cells. He plans to develop sheets of islets and surgically place them in the abdominal tissue of three people with type 1 diabetes, who will receive immunosuppressants. The first participant should receive their transplant early next year.
矢部也即将开始一项使用供体iPS细胞生产的胰岛细胞的试验。他计划培育成片的胰岛细胞，并通过手术将其植入三名1型糖尿病患者的腹部组织，这些患者将接受免疫抑制剂治疗。第一位参与者将于明年初接受移植。