Cell Stem Cell:鼓动人心!更新更有效的干细胞移植方法可以帮助血癌患者

2020-03-28 竹子 转化医学网

近日,伦敦大学学院(UCL)的研究人员已经开发出一种使脐带血中的干细胞“更易于移植”的新方法,这一发现在小鼠中可以改善对儿童和成人多种血液疾病的治疗。这项研究发表在《细胞干细胞》杂志上。

血液干细胞,也称为造血干细胞(HSC),可在血液中产生每种类型的细胞(红细胞,白细胞和血小板),并在整个生命中维持血液的产生。在治疗某些癌症和遗传性血液疾病时,有时有必要通过同种异体干细胞移植来替代骨髓,这涉及使用健康供体的干细胞。如今,研究人员正在寻找更易于移植的方法。

近日,伦敦大学学院(UCL)的研究人员已经开发出一种使脐带血中的干细胞“更易于移植”的新方法,这一发现在小鼠中可以改善对儿童和成人多种血液疾病的治疗。这项研究发表在《细胞干细胞》杂志上。这一发现潜在地为所有年龄段的患者打开了一扇门,让他们都能使用那些原本会被丢弃的医疗设备。

所述脐带是血液干细胞的有用来源,和导致比脐带血移植移植更少长期免疫并发症。尽管近30年来,脐带血移植已在幼儿中使用,但大多数脐带血单位的HSC均不足以适合年龄较大的儿童和成人,而所有脐血单位中的30%甚至对于最小的儿童而言都太少了,浪费掉了。

UCL癌症研究所临床副教授,该研究的第一作者Rajeev Gupta博士解释说,试图增加脐带血中造血干细胞的实际数量既昂贵又具有挑战性。并非脐带血单位中存在的所有HSC都能或将会移植,这表明脐带血单位具有尚未开发的移植潜能。

研究人员探索了一种替代方法,通过增加HSC的功能(而非数量)来利用这种潜力,从而提高脐带血单位移植能力。

他们先前发现一种称为NOV的调节蛋白对于人类HSC的正常功能至关重要,因此在思考是否可以使用高纯度的NOV来操纵脐带血HSC使其具有更高的可移植性。

NOV标记细胞

(A)在SFEM加STF或STF + Alexa Fluor 488-NOV中孵育8 h的UCB CD34 +细胞中NOV结合的流动直方图。

(B)用于NOV标记和未标记NOV的CD34 +细胞的细胞分选的密度图。

UCL癌症研究所的研究小组在实验室中使用细胞培养物和小鼠模型,发现暴露于NOV的脐带血单位显示出比常规样品明显更高的移植潜力。实际上,样品中功能性HSC的频率增加了六倍。令人惊讶的是,这些效果仅需暴露8小时即可达到。

(C)UCB CD34 + 38-lin-隔室的90-RA +,90-RA-和90 + RA-部分中NOV标记细胞的百分比。在抗体染色之前,将CD34 +细胞用NOV标记8小时。平均值+ SEM;n = 3。

(D)密度图显示在UCB CD34 + 38-90 + 45RA + Lin-隔室中NOV标记的细胞和CD49f +细胞的共分离。

安东尼·诺兰研究所科学主任,干细胞移植领域的世界领先科学家亚历杭德罗·马德里格教授评论,使用NOV已经证明可以快速操纵血液干细胞以改变其状态-将无功能的HSC转变为有功能的HSC-增强了脐血的植入潜力。这一发现为改善血液移植提供了新的策略。现阶段将是把研究纳入临床,以探索这将如何使患有血液癌和其他血液疾病的患者受益。

研究证明,脐血移植可以改善移植并为许多人提供更好的结果。但是,许多脐带血单位中的干细胞数量可能不足以实现最佳移植。这项研究很鼓动人心,因为只需添加NOV / CCN3,现有干细胞的功能就会增加。这种实用的解决方案可以使更多的具有有限干细胞数量的脐带血单位可用于移植,并可能对许多患者产生巨大的影响,值得在临床环境中进行进一步研究。

原始出处:Rajeev Gupta, Turati V, Brian D, et al. Nov/CCN3 Enhances Cord Blood Engraftment by Rapidly Recruiting Latent Human Stem Cell Activity. Cell Stem Cell.19 March,2020.

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    2020-08-25 docwu2019
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    2020-03-31 独孤立克

    干细胞是热点,但是进入临床仍然需要时间和临床疗效验证哦

    0

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    2020-03-29 liuhuangbo

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婴儿急性淋巴细胞白血病(ALL)是一种罕见的白血病,在年长儿童中KMT2A基因重排仅有1%~2%,但在婴儿中出现概率可达75%左右。为了解决相关的治疗问题,需要大规模的国际合作。近期发表在JCO 杂志上的一项国际III期随机研究Interfant-06试图探索在1岁以下婴儿急性淋巴细胞白血病的治疗,让我们一起来看看吧。