Nat Bio Eng:一项新技术能在体内产生胰岛素,治疗糖尿病

2020-04-02 Lauren 转化医学网

导言:糖尿病是一组因胰岛素绝对或相对分泌不足(或)胰岛素利用障碍引起的碳水化合物、蛋白质、脂肪代谢紊乱性疾病,以高血糖为主要标志。目前尚无根治糖尿病的方法,但通过多种治疗手段可以控制好糖尿病,主要包括

导言:糖尿病是一组因胰岛素绝对或相对分泌不足(或)胰岛素利用障碍引起的碳水化合物、蛋白质、脂肪代谢紊乱性疾病,以高血糖为主要标志。目前尚无根治糖尿病的方法,但通过多种治疗手段可以控制好糖尿病,主要包括5个方面:糖尿病患者的教育,自我监测血糖,饮食治疗,运动治疗和药物治疗。

糖尿病的典型临床表现为“三多一少”,即多饮、多尿、多食和体重下降,以及血糖高、尿液中含有葡萄糖等,病程久可引起多系统损伤,导致眼、肾、神经、心脏、血管等组织器官的慢性进行性病变、功能减退及衰竭,病情严重或过激时可引起急性严重代谢紊乱。糖尿病是导致心脑血管疾病、死亡、截肢、失明、肾功能衰竭和心力衰竭的重要原因。

治疗糖尿病的一个有希望的方法是移植胰岛细胞,当血糖水平过低时,胰岛细胞就会产生胰岛素。然而,接受这种移植的患者必须服用药物,以防止免疫系统对移植的细胞产生排斥,因此这种疗法并不常用。

为了使这种疗法更可行,麻省理工学院的研究人员现在已经设计出一种方法,将治疗细胞封装在一种灵活的保护装置中,这种装置可以防止免疫排斥,同时还允许氧气和其他重要的营养物质进入细胞。这种细胞可以在任何有需要的时候分泌胰岛素或其他蛋白质。

化学工程副教授、麻省理工学院科赫综合癌症研究所(Koch Institute for Integrative Cancer Research)和医学工程与科学研究所(Institute for Medical engineering and Science)成员、该研究的资深作者丹尼尔·安德森(Daniel Anderson)说,“我们的设想是建立一个活的药厂,你可以把它植入病人体内,它可以根据病人的需要分泌药物。我们希望这样的技术可以用于治疗许多不同的疾病,包括糖尿病。”

在一项对小鼠的研究中,研究人员发现,经过基因工程改造的人类细胞至少能存活5个月,而且他们相信,这些细胞可以持续更长时间,以实现对糖尿病或血友病等慢性疾病的长期治疗。

科赫研究所的研究科学家苏曼·博斯是这篇论文的主要作者,该论文在2020年3月31日发表在《自然生物医学工程》杂志上。

保护作用

1型糖尿病患者通常每天要注射几次胰岛素,以保持他们的血糖水平在一个健康的范围内。自1999年以来,一小部分糖尿病患者接受了胰岛细胞移植,这些胰岛细胞可以替代失去功能的胰腺。虽然治疗通常是有效的,但这些患者必须服用的免疫抑制剂药物使他们易受感染,并可能产生其他严重的副作用。

几年来,安德森的实验室一直在研究保护移植细胞不受宿主免疫系统影响的方法,这样就不需要使用免疫抑制剂了。

安德森说:“我们希望能够将细胞植入能够分泌胰岛素等治疗因子的病人体内,但又能防止它们被身体排斥。”“如果你能制造一种不需要免疫抑制就能保护这些细胞的设备,你就能真正帮助很多人。”

为了保护移植的细胞免受免疫系统的伤害,研究人员将它们安置在一个由硅基弹性体(聚二甲基硅氧烷)和一种特殊多孔膜构成的装置中。博斯说:“它几乎和组织一样坚硬,你把它做得足够薄,这样它就能包裹住器官。”

然后他们在设备的外表面涂上一种叫做THPT的小分子药物。在之前的一项研究中,当免疫系统攻击外来物,研究人员发现这种分子可以帮助防止纤维化,即疤痕组织的形成。该设备包含一个多孔膜,允许移植的细胞从血液中获取营养和氧气。这些气孔必须足够大,使营养物质和胰岛素得以通过,但又必须足够小,使T细胞等免疫细胞无法进入并攻击被移植的细胞。

在这项研究中,研究人员测试了直径从400纳米到3微米的聚合物涂层,发现800纳米到1微米的尺寸范围是最理想的。在这种大小下,小分子和氧气可以通过,但T细胞不能。到目前为止,人们一直认为1微米的气孔太大,无法阻止细胞的排斥反应。

对药物的需求

在一项对糖尿病小鼠的研究中,研究人员发现,这项技术可以在小鼠体内维持健康血糖水平超过10周。另外,研究人员还对人类胚胎肾细胞进行了测试,这些细胞被改造成拥有产生促红细胞生成素(EPO)的能力。据悉,这种激素能够促进红细胞生成素的产生。这些封装的细胞在被移植到小鼠体内后存活了19周以上,从而使得整个红细胞计数得到增长。

此外研究小组还发现,被包裹的细胞可能被某些特定的药物触发从而产生某些蛋白质。在一项实验中,科学家们让老鼠服用强力霉素后细胞才开始产生促红细胞生成素,这表明该技术可以作为一种“活药厂”,按需提供所需的激素和蛋白质。

研究人员说,这种“活药厂”可以用于治疗任何需要经常服用蛋白质或激素的慢性疾病。他们目前正专注于糖尿病,并致力于延长移植胰岛细胞的寿命。

“这是我们团队在过去4年多的时间里发表的第8篇自然杂志论文,阐明了植入物生物相容性的关键基础方面。我们希望并相信,这些发现将在未来几年为治疗糖尿病和许多其他疾病带来新的超级生物相容性植入物,”麻省理工学院戴维·h·科赫研究所(David H. Koch Institute)教授、论文作者之一罗伯特·兰格(Robert Langer)说。

原始出处:

Suman Bose, Lisa R. Volpatti, Devina Thiono, et.al. A retrievable implant for the long-term encapsulation and survival of therapeutic xenogeneic cells. Nature Biomedical Engineering 30 March 2020

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    2020-06-25 sunylz
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    2020-05-31 liye789132251
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    2020-11-07 baoya
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    2020-12-15 spoonycyy
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    2020-04-02 misszhang

    谢谢MedSci提供最新的资讯

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