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SCI ADV:新胰岛移植术有望使糖尿病患者彻底摆脱外源胰岛素治疗!

2017-06-05 佚名 medicalxpress

【新的移植技术使1型糖尿病患者获益】将新的水凝胶材料与促进血管生长的蛋白质结合可以提高将生产胰岛素的胰岛细胞移植到1型糖尿病患者体内的成功率。在动物模型中,该技术提高了移植胰岛素生产细胞的存活率,恢复胰岛素产生以响应于血糖水平和治愈这些糖尿病动物。

【新的移植技术使1型糖尿病患者获益】将新的水凝胶材料与促进血管生长的蛋白质结合可以提高将生产胰岛素的胰岛细胞移植到1型糖尿病患者体内的成功率。在动物模型中,该技术提高了移植胰岛素生产细胞的存活率,恢复胰岛素产生以响应于血糖水平和治愈这些糖尿病动物。


该技术还可以帮助因严重胰腺炎(一种炎症性疾病)而将胰腺切除的病人。研究人员利用该材料和蛋白质组合评估了多个位置,用于植入胰岛细胞簇,这是首次直接比较移植部位。

乔治亚理工学院机械工程学院院士安德里斯·加西亚(AndrésGarcía)说:“我们设计了一种可用于移植胰岛并促进胰岛血管化和生存以增强其功能的材料。 “我们对此感到非常兴奋,因为如果这证明在人类中取得成功,那么可以立即使病人获益。”


研究由少年糖尿病研究基金会和国家卫生研究院所支持,6月2日在科学进步杂志上报道。


1型糖尿病影响数百万人

约有125万美国人患有1型糖尿病,也称为青少年糖尿病,一种以身体不能产生胰岛素为特征的疾病。为了控制疾病,患者必须经常测试其葡萄糖水平并注射胰岛素以保持适当的平衡。但有些病人会出现危及生命的低血糖发作,而且这种疾病还会带来其他严重的健康后果。

使用尸体细胞,医生已经将胰岛实验性移植到人类中了数十年,但是多达60%的移植胰岛因为血液供应被切断而直接注入血液,从而被免疫系统攻击死亡,而那些在移植中存活的通常会在几个月内死亡。在迄今进行的测试中,胰岛已经被放置在肝脏的脉管系统中,其具有显着的血液供应 - 但是由于敌对的免疫环境可能这并不是理想的位置。

设计新的解决方案

所以García和合作者,包括佐治亚理工博物馆博士后研究员和第一作者杰西卡·韦弗(Jessica Weaver),开始设计一种移植细胞的新方法。他们开发了一种新的可降解聚合物水凝胶材料,用于在细胞注射入体内时递送细胞。并且它们在凝胶中掺入称为血管内皮生长因子(VEGF)的蛋白质,其促进血管进入移植细胞的生长

García还说:“移植的胰岛需要大量的氧合和与身体循环系统的连接,以感测葡萄糖水平和运输胰岛素。除了保护胰岛之外,我们的工程材料还促进了新血管的形成以滋养细胞。”

VEGF已经被尝试过,但是量太大,它刺激了不提供长期氧合的泄漏血管的生长。血管内皮细胞数量太少,不能快速生长血管以维持移植的胰岛存活,这些胰岛是含有数百个细胞的簇。在群集中没有足够的脉管系统,中心的细胞不能存活。

制造者使用糖尿病小鼠来比较体内可以放置移植细胞的位置。她研究了肝脏,皮肤下的位置,肠道附近的肠系膜和腹部附睾脂肪。

可能治疗更多的病人

Weaver说:“我们能够平行研究移植站点,并且真正地考察每个移植站点的利弊来比较每个区域的细胞存活率。 “胰岛细胞是非常宝贵的,因为我们每个供体都很少,我们需要他们生存,帮助1型糖尿病患者脱离胰岛素。”


在肝脏位置,现在需要多达三个供体来获得足够的可移植胰岛以在单个患者中提供葡萄糖控制。 García指出,如果研究人员可以减少细胞损失,那么有可能有一天可以通过有限数量的尸体捐献者来治疗两倍甚至三倍数量的患者。


评估技术

韦弗研究了动物模型长达100天,发现移植有水凝胶和VEGF的胰岛群发展出许多血管并植入新的位置。如预期的那样,水凝胶材料消失,并被围绕胰岛生长的新组织代替。

为了跟踪胰岛细胞的长期存活力,她在用特定波长的光激发时使用具有产生绿色发光的基因的细胞。通过测量从移植位置返回的信号,她能够确定有多少细胞存活。在血液中引入染料,然后允许她对胰岛周围的血管进行成像。

腹部脂肪垫原来是提供最佳的移植位置。在人类中,等效结构称为网膜,其他研究人员正在评估为血小板移植位置的血管丰富的区域。如果将该技术用于人类,则可以在微创手术中将细胞置于腹腔镜下。水凝胶将以液体形式注射,并在移植部位聚合,产生符合身体结构的柔性凝胶,以改善血管连接和组织整合。

下一步是什么?

作为下一步,加西亚和韦弗想研究大型动物的技术。之后,需要进行人体临床试验,以显示水凝胶材料和蛋白质的组合是否会使1型糖尿病患者受益。最终,研究人员希望干细胞可能提供可以被移植而不需要尸体供体胰岛和免疫系统抑制的胰岛来源。

在加入佐治亚理工大学之前,糖尿病研究所的研究员韦弗(Dr. Waver)表示,她对新技术的运行情况感到惊讶。该成像提供了围绕胰岛团的不断增长的血管系统的清晰视图。


韦弗说:“当我们第一次开始做成像时,我很确定我第一次看到它时尖叫。 “看到脉管系统太美了,我并没有想到能看到这种完美的血管生长进入胰岛。”

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    2018-04-12 cy0324
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    2018-05-22 baoya
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    2017-06-06 哈夫

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