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Cell Stem Cell:肠道也可以造血!追踪21名肠移植患者5年后,哥大科学家发现人类肠道生产的血细胞占到全身的10%

2018-12-04 奇点糕 奇点网

近期《细胞干细胞》上刊登了一项来自哥伦比亚大学的研究,研究者发现,肠道中也有造血干细胞和祖细胞(HSPCs),而且与骨髓中的类似,都具有多分化和自我更新的能力!研究者追踪了21个做了肠移植的患者5年,发现这些细胞竟然还有助于促进移植组织的免疫耐受!

近期《细胞干细胞》上刊登了一项来自哥伦比亚大学的研究,研究者发现,肠道中也有造血干细胞和祖细胞(HSPCs),而且与骨髓中的类似,都具有多分化和自我更新的能力!研究者追踪了21个做了肠移植的患者5年,发现这些细胞竟然还有助于促进移植组织的免疫耐受!

目前我们还不清楚肠道到底能够提供多少血细胞,但根据研究者的估计,比例应当不低于全循环系统的10%!


通讯作者Megan Sykes

对于肠衰竭晚期的患者来说,肠移植就是唯一的手段了。肠移植失败率很高,5年失败率约为50%。约有5-9%的患者会发生移植物抗宿主病(GVHD),这是由移植组织中含有的大量淋巴细胞对受者产生免疫反应造成的。

讲道理,如果GVHD是由供者淋巴细胞造成的,那么按理说供者淋巴细胞越少越不容易发生对不对?可是实际情况却截然相反!研究者们在2015年曾做过一项研究,发现早期发生严重排斥反应的患者反而供者血细胞水平更低,而且多器官联合移植也并不比肠单独移植排斥风险更高。

奇怪,反而像是供者淋巴细胞越多越安全呢!



在此前研究的基础上,研究者又招募了一批患者,对总计21名接受了肠移植的患者进行了5年的跟踪研究。令人惊讶的是,在很长一段时间里,甚至移植后4年,患者的外周血中都一直存在着自身和供者两种类型的血细胞。

研究者检查了这些来自供者的血细胞,发现来自供者的T细胞很明显曾经去过受者的胸腺。胸腺是T细胞发育成熟的“学校”,咋的,这些外来户还去进修过?

经过进一步分析,原来这些长期存在的T细胞竟然真的不会导致GVHD,而且还另有功能,经过受者胸腺的训练,和受者的组织以及免疫器官达成和平共处条约,甚至还能帮助移植组织耐受。

咱们还以为移植之后免疫细胞之间要有一场攻城略地的战争,岂知人家早就通过外交手段解决了问题!


以脾中免疫细胞为对照检查了供者T细胞的特征

其实2006年就有科学家发现小肠中存在造血干细胞和淋巴祖细胞了,当时的研究只解决了和肠道中淋巴细胞分化有关的一些困惑。

研究者也对肠道中的造血干细胞和祖细胞(HSPCs)进行了检测,HSPCs广泛分布于肠黏膜、派尔集合淋巴结、肠系膜淋巴结和肝脏中,而且这些HSPCs于骨髓来源的HSPCs表型很相似。

研究者先是把两种来源的HSPCs拿到体外培养,结果显示二者形成的细胞群很相似。在人源化小鼠中进行的移植实验结果也证实,肠道中的HSPCs能够分化为NKT、CD4+T、B细胞、单核细胞等淋巴细胞,具有和骨髓HSPCs一样的多方向分化潜能,同时也具有自我更新能力。

当然,最后这些来自供者的HSPCs还是会逐渐被循环系统中受者的HSPCs替代掉的。


“外交”始末

从结果来看,有更多供者血细胞的患者更不容易产生排斥反应,这意味着器官移植可能会迎来一些新的观点。通讯作者Megan Sykes指出,有大量供者细胞的患者可能不需要现在这么多的免疫抑制剂,减少免疫抑制剂本身也是对预后有好处的。

另外,器官移植之余提供供者的造血干细胞移植或许也可以增加供者和受者之间的免疫交互,增加移植器官的耐受性。研究者下一步准备开展相关的临床研究,希望可以通过增加供者血细胞水平提高免疫耐受、减少免疫抑制药物的使用。

原始出处:Jianing Fu, Julien Zuber, Mercedes Martinez, et al. Human Intestinal Allografts Contain Functional Hematopoietic Stem and Progenitor Cells that Are Maintained by a Circulating Pool. Cell Stem Cell. November 29, 2018

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    2018-12-11 维他命
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    2018-12-05 俅侠
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    2018-12-05 kafei

    学习了谢谢

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