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日本通过胰岛细胞移植治愈Ⅰ型糖尿病患者

医案日记 2023-06-15 22:20:46

日本通过胰岛细胞移植治愈Ⅰ型糖尿病患者

据《读卖新闻》17日报道,今年4月和7月在日本京都大学附属医院两次接受胰岛细胞移植的一名女性Ⅰ型糖尿病患者,16日被宣布完全康复。

据报道,该名女性患者34岁,14岁时被诊断患有Ⅰ型糖尿病。20年来,患者每日必须注射4次胰岛素。

京都大学附属医院今年4月从一名心脏停止跳动的男性胰脏中分离出35万个胰岛细胞,移植到该女性患者体内后,患者开始分泌胰岛素。7月初,该患者又接受手术,移植了从另外一名捐献者的胰脏里分离出的40万个胰岛细胞。

之后的检查结果显示,该名女性患者已能正常分泌胰岛素。

据悉,患者已于8月初出院,现在只需服用免疫抑制剂。

统计表明,利用从脑死亡者提供的胰脏中分离出的胰岛细胞进行移植,这样的手术目前世界上已有约500例。

但根据日本的脏器移植法,脑死亡者不能作为脏器捐献者,只能利用心脏停止跳动者捐献的脏器,因此类似的胰岛细胞移植术在日本仅有4例。

胰岛细胞移植只需进行30分钟点滴,不必进行开胸手术,可以大大减轻患者的负担。日本国内Ⅰ型糖尿病患者约为14万人,这次该名患者的成功治愈为Ⅰ型糖尿病患者带来了希望。

细胞移植治疗糖尿病遇尴尬

Diabetes Treatment Disappoints in New Study

细胞移植法治疗糖尿病遭遇尴尬

The cell transplants did free patients from insulin shots, but only temporarily: within two years, 86 percent needed insulin again, according to a report to be published Thursday in The New England Journal of Medicine.

星期四刊登在《新英格兰医学杂志》上的报告显示,细胞移植的确免除了患者注射胰岛素之苦,但是作用却只是暂时的:86%的患者在2年以内再次需要新的胰岛素。

The patients had severe Type 1 diabetes, also called juvenile diabetes, in which the body lacks insulin and people must inject it several times a day to control blood sugar. They were given islet cells from the pancreas of a dead organ donor.

患有严重的I型糖尿病,也称为青少年糖尿病的患者体内缺少胰岛素,为了控制血糖必须每天多次注射胰岛素。他们被移植了死亡的器官捐献者的胰脏细胞。

The transplants do not require major surgery, just a tube inserted into a vein in the abdomen so that the cells can be dripped into the liver, where they take up residence in tiny blood vessels. Because the transplanted cells come from someone else, recipients must take immune-suppressing drugs for life to prevent rejection.

移植手术不需要动大手术,只需要在患者腹部的血管中插入一个导管把细胞倒入患者的肝脏,细胞就依附在肝脏细小的血管上。因为细胞来自于别人体内,接受移植的患者必须终生服用免疫抑制药物,预防产生排异现象。

The study, involving 36 patients at nine centers in the United States, Canada and Europe, was inspired by a smaller trial published in 2000 that sparked excitement about a transplant technique called the Edmonton protocol, developed at the University of Alberta. In that initial test, none of the patients needed insulin shots-but when the report was published, none had been followed for more than 14 months. Later, many did need the shots again.

这项研究是在来自于美国、加拿大和欧洲9个中心的36名患者身上进行的。研究受到2000年发布的一项小规模的试验结果的启发,那一试验提出了让人兴奋的移植技术,即在埃尔伯塔大学发展起来的埃德蒙顿方案。在起初的试验中,没有一个患者需要注射胰岛素。但是到试验报告发布的时候,所有的病人跟踪观察还不到14个月。后来,许多患者还是需要接着注射胰岛素。

In the newer study, the transplants failed completely within a year in 10 of the 36 patients; but 16 others were off insulin completely, and the remaining 10 needed less insulin than before. By two years, only five were still free of insulin shots. A quarter of the patients had to switch immune-suppressing drugs because of side effects, which sometimes included a drop in kidney function.

在新近的研究中,在细胞移植的36例患者中,1年以内有10例移植完全失败;但是另外16例患者完全不在需要胰岛素注射,另外10例需要的胰岛素的量也比以前减少了。到2年的时候,仅有5例依然不需要注射胰岛素。由于副作用的原因,包括出现肾功能下降的情况,四分之一的患者不得不停止使用免疫抑制药物。

For now, the cell transplants are not recommended for most patients.

所以现在绝大部分患者都没有建议采用细胞移植法。

"I don't think this is ready for prime time," said Dr. Jonathan S. Bromberg, director of transplantation at Mount Sinai Hospital in Manhattan. He was not involved in the research, but wrote an editorial about it in the same journal.

“我认为时机还不成熟,” 曼哈顿西奈山医院器官移植主任乔纳森·S·布隆伯格博士说。他没有参与这次研究,但是他在同一期刊上撰写了关于研究报告的社评。

But he also said the field was advancing so fast that the transplants may actually become a viable option in the not-so-distant future.

但是他说,这一领域发展很快,实际上移植可能在不远的将来成为可靠的治疗方法。

"I think we've got every reason to believe there will be significant progress," Dr. Bromberg said.

他表示:“我认为我们有足够的理由相信这一技术将会取得重大的进步。”

In the meantime, even in their present form, the cell transplants may still help some people - approximately 10 percent of those with Type 1 diabetes, who frequently suffer from severe episodes of low blood sugar, or hypoglycemia, that strike without warning and can cause confusion, fainting or even seizures.

同时,即便是在他们现在的情形下,细胞移植对于大约10%的患有I型糖尿病的患者可能依然有用。这些患者经常受到严重的低血糖症状或者低血糖症的折磨,这些疾病会在没有任何征兆的情况下发生,并能诱发神志不清、昏迷甚至惊厥。

This kind of hypoglycemia can be so severe that patients "can't function in society," said Dr. A.M. James Shapiro, who led the study and is director of the islet transplant program at the University of Alberta. His team developed the Edmonton protocol.

这种低血糖症会非常严重,可以导致患者“不能正常活动”,领导这项研究的埃尔伯塔胰岛移植项目主任A.M. 詹姆斯·夏皮罗博士表示。他领导的团队开创了埃德蒙顿方案。

Patients in the study had the condition, but the transplants diminished their hypoglycemic attacks, even when the cells were only partly effective.

研究中的患者都有上述情况,但在细胞移植后,甚至即便在这些细胞只有部分发挥作用时,他们都免受了低血糖症的困扰。

In the United States, the cell transplants are considered experimental and are available only in studies. They are more widely available in Canada, Dr. Shapiro said.

在美国,细胞移植还在试验阶段,只有在研究中可以使用。夏普罗博士介绍说,但在加拿大,细胞移植应用更加广泛。

Transplanting the entire pancreas can reverse Type 1 diabetes, but it is a major operation and in this country is usually done only when the diabetes is so severe that the patient needs a kidney transplant as well. About 1,500 pancreas transplants a year are performed in the United States. The transplants tend to work for 5 to 10 years, Dr. Bromberg said. Eventually most patients need insulin again.

完全移植整个胰脏可以彻底治疗I型糖尿病,但是这是一项大手术,而且在美国只有糖尿病已经严重到需要肾移植的时候才通常会被采用。布隆伯格博士说,移植往往可以保证5到10年,但大多数患者最后还是需要注射胰岛素。

But people with Type 1 do not really need a whole pancreas: they need just the islet cells, which make up only about 3 percent of the organ.

I型糖尿病患者并不是一定需要整个胰脏的移植,他们只需要相当于整个器官3%的胰岛细胞。

Researchers have been experimenting with islet transplants since the 1970's. But the cells never survived for long in humans - not until the study reported in 2000 by Dr. Shapiro and his colleagues. His team succeeded because they suspected that the immune-suppressing drugs were killing off the islet cells, and they switched to a less toxic regimen. It worked.

研究人员从20世纪70年就开始试验胰岛细胞移植。但是直到2000年夏普罗博士和他的同事发表的研究报告,这些细胞在人体内从来就没有存活过。他的研究小组的成功是由于他们怀疑抑制免疫的药物同时也杀死了胰岛细胞,所以他们成功地使用了一种毒性更小的疗法。

Even so, too many cells die - half to three quarters, Dr. Shapiro said. If more could survive, patients might be able to go much longer without insulin. Researchers are testing different drug combinations and other refinements to improve their results.

夏普罗博士说,即便如此,太多的细胞-大约有一半岛3/4,还是死亡了。如果更多的细胞能够存活,患者不需要使用胰岛素的时间就可能会延长。研究人员正在试验不同的药物组合和其他的更加精细的方法来提高细胞的成活率。

"I would be first to admit that it has a long way to go before it matches whole pancreas transplantation," Dr. Shapiro said, but he added that he still expected the cell infusions to catch up with whole organ transplants in a few years. The shortage of organ donors will be a limiting factor, however.

“首先我得承认,要达到整个胰脏移植的效果还有很长的路要走,”夏普罗博士承认,但是他接着说,他依然期待在几年的时间里细胞灌输可以赶上整个胰脏器官移植的效果。然而,缺少胰脏捐献者将是一个不利因素。

Dr. Bromberg said that for most diabetics, new forms of insulin, insulin pumps and glucose monitors were improving control of the disease so much that it would be hard to justify the risks of a transplant and lifelong immune-suppressing drugs.

布隆伯格博士说,对于大多数糖尿病患者,新的合成胰岛素、胰岛素泵和血糖监测仪大量使用,用来改善对疾病的监控,但这也使得判断细胞移植和终生使用免疫抑制药物的风险变得困难。

Cell transplants are being studied primarily in people with Type 1 diabetes, which affects about a million people in the United States. It occurs when a person's immune system, for unknown reasons, attacks the pancreas cells that make insulin.

细胞移植的研究首先是在I型糖尿病患者身上进行的,患这种疾病的人在美国大约有100万人。这一疾病是由于某种不确知的原因致使免疫系统损害产生胰岛素的胰岛细胞所致。

Type 2 diabetes is different, and far more common, affecting about 20 million in the United States. Patients produce insulin, but their bodies cannot use it properly. The disease is genetic, but often develops only when someone who has the genes for it also becomes overweight. Type 2 is increasing in many countries as obesity rises. (Type 1 is not linked to obesity.)

II型糖尿病则不同,也更加普遍,在美国大约有2000万患者。患者能够分泌胰岛素,但却不能正常地使用这些胰岛素。这种疾病是遗传所致,但是通常只在带有致病遗传基因同时也体重超标的人才会患这种疾病。II型糖尿病随着肥胖症的增加在很多国家也有所增加。I型糖尿病与肥胖症无关。

Both forms of the disease can have devastating consequences, including blindness, kidney failure and circulatory problems that can lead to amputations.

两种疾病都可能导致灾难性的后果,包括失明、肾衰竭和导致的截肢的循环系统疾病。

干细胞移植可以治疗糖尿病吗

?干细胞移植目前属于临床研究阶段还不能用于治疗,如果是一型糖尿病,胰岛素是最好的治疗方案。 糖尿病病人尽早实施胰岛素治疗,可使血糖长期严格控制达标,大大减少糖尿病慢性并发症(尤其是微血管并发症)的发生率。而且,给予适量的胰岛素治疗,有利于维持正常的糖代谢和脂代谢,改善胰岛素抵抗,对心血管具有保护作用。 借助特定类型的干细胞可调节机体的免疫功能,因而尝试使用干细胞治疗免疫系统疾病已成热门,其中就包括1型糖尿病。 有胰岛素还不够 1型糖尿病为儿童及青少年最常见的内分泌疾病之一,随病程进展,患者胰岛β细胞数目进行性减少甚至完全丧失,功能随之殆尽。临床上主要通过外源胰岛素的替代治疗来维持患者体内正常的血糖水平。但是长期皮下注射胰岛素在一定程度上可以延长或维持生命,却不能阻止并发症发生,还会带来较严重的身心问题,降低其生活质量。因此,医生仍在探求新方案,以期实现或接近理想化目标,即摆脱外源性胰岛素的替代治疗。 借干细胞调节免疫 现已认同1型糖尿病是T淋巴细胞介导的自身免疫性疾病,其发生与自身反应性T细胞激活并增殖,选择性破坏胰岛β细胞有关。因此消除异常的免疫反应,重建一个正常的免疫系统,才可能治愈1型糖尿病。目前可选的思路一方面是阻止胰岛β细胞继续破坏,保护残留胰岛β细胞;另一方面是促进胰岛β细胞增殖。 干细胞作为人体各种组织细胞的初始来源,其最显著的生物学特征是既有自我更新和不断增生的能力,又有多向分化的潜能。而特定类型的干细胞还可同时调节机体的免疫功能。目前,临床干细胞移植在治疗其他自身免疫性疾病,如系统性红斑狼疮、多发性硬化等方面均取得了良好效果。而探索干细胞移植技术已成为全球糖尿病治疗领域的一个新亮点,也引起了前所未有的关注。 临床尝试确有效果 自体外周造血干细胞移植治疗1型糖尿病的可能机制,是在免疫病理细胞清除的基础上重建相对正常的免疫系统,并可能形成新的免疫耐受;同时通过不同途径促使胰岛β细胞增殖,使胰岛素水平达到或接近正常的分泌状态。 基于这种治疗机理,国外学者Voharelli等采用自体外周造血干细胞移植的方法治疗了新诊断的1型糖尿病患者,并在不同时期内停用外源性胰岛素,证实造血干细胞移植治疗1型糖尿病具有良好效果,且移植距发病的时间对于移植后病情的改善有重要影响。 大规模推广还太早 需要指出的是,无论是自体造血干细胞还是间充质干细胞移植治疗糖尿病,都仅是初步探索。尽管取得了一些令人鼓舞的结果,但其中也存在不少问题仍待进一步探索和确定。因此,目前干细胞移植治疗糖尿病仍处于临床探索阶段,不宜大规模推广使用,前述一些研究仅仅是短期疗效评估,而且样本量相对较少,其确切疗效尚需大样本、长期随访进一步确定。然而,国内一些医院却盲目夸大干细胞移植治疗糖尿病的疗效,或由于经济利益的驱使,对可能并不适合移植的患者采用了这种方法,有悖科学原理,显然不应提倡。 干细胞移植可以治疗糖尿病目前虽然有些进展,但还远未成熟。建议能在有经验的医生指导下找到适合自己病情的胰岛素的剂型剂量和用法,祝您健康! 相关阅读:干细胞治疗肝硬化及糖尿病问题与回答 糖尿病

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