《自然》发现：伤害性感受神经元有助于调节造血干细胞动员

编辑翻译：菁菁

译文校对：奇奇

来自阿尔伯特·爱因斯坦医学院和北卡罗来纳大学教堂山分校的研究团队发现，骨髓中的伤害性感受神经元（HSC）有助于调节造血干细胞动员。该团队总结了它们的工作，并发表在《自然》杂志上。他们试图更多地了解骨髓中发现的伤害感受神经。多伦多大学健康网络的Anastasia Tikhonova博士和纽约大学格罗斯曼医院的Iannis Aifantis博士分别就这一研究成果发表了新闻和评论文章。

造血前体细胞：早幼粒细胞位于图片中心，其旁边有两个间质骨髓细胞，以及来自骨髓的带状细胞。

正如Tikhonova博士和Aifantis博士所指出的，造血干细胞起源于骨髓，它们增殖分化成血细胞和免疫细胞，并经由造血过程进入血液。在动员之前，HSC位于骨髓内部的特殊处所中——它们仅在需要时动员。对于接受白血病和其它血液癌症治疗的人群，医师使用特殊药物从骨髓中收集HSC，并在化疗期间进行保存。化疗完成后，将保存的HSC替换回患者体内，以补充治疗过程中损耗的免疫细胞。不幸的是，在一些人群中，因为HSC拒绝被吸引出自己所在的处所，可能会因收集HSC而出现问题。在这一项目中，研究团队对骨髓中的伤害性感受神经元开展研究，旨在了解它们为什么存在于骨髓中。在人体的其它部位，如皮肤，它们的作用是感知疼痛。研究人员发现它们在造血干细胞动员中发挥作用。

本研究中，该团队使用免疫荧光成像技术研究了小鼠骨髓中的神经细胞，发现其中大多数是伤害性感受神经元。这一发现使研究人员想要知道这些神经是否在造血干细胞动员中发挥作用。为了证实情况是否如此，他们使用药物和基因工程技术，以两种方式禁用了这些神经元。他们发现这样做对HSC水平的维持没有影响，但是确实导致导致造血干细胞动员大幅减少。然后，研究人员尝试给小鼠提供药物，以促使与HSC相关的神经递质产生。他们发现，这样做可以增加造血干细胞的动员。此外，研究人员对老鼠辣椒素（一种存在于辣椒中的成分）进行了研究，并发现它也增加了造血干细胞动员。

英文原文

Nociceptive nerves found to help regulate hematopoietic stem cell mobilization 

A team of researchers from the Albert Einstein College of Medicine and the University of North Carolina at Chapel Hill has discovered that nociceptive nerves found in bone marrow help to regulate hematopoietic stem cell mobilization. In their paper published in the journal Nature, the group describes their work, in which they attempted to learn more about nociceptive nerves found in bone marrow. Anastasia Tikhonova and Iannis Aifantis with the University Health Network, Toronto and New York University's Grossman School of Medicine, respectively, have published a News and Views piece on the work done by the researchers in the same journal issue.

Hematopoietic precursor cells: promyelocyte in the center, two metamyelocytes next to it and band cells from a bone marrow aspirate. Credit: Bobjgalindo/Wikipedia

As Tikhonova and Aifantis note, hematopoietic stem cells (HSCs) originate in bone marrow—they grow into blood and immune cells, which make their way into the bloodstream via a process called hematopoiesis. Prior to mobilization, HSCs reside in special niches inside of bone marrow—they only mobilize when needed. In people being treated for leukemia and other blood cancers, HSCs are collected from the bone marrow using special drugs and stored for the duration of chemotherapy. Then the HSCs are replaced so that they can replenish the immune cells that were lost. Unfortunately, in some people, collecting HSCs can be problematic because the HSCs refuse to be enticed out of their niches. In this new effort, the researchers were studying nociceptive nerves in bone marrow hoping to learn why they exist in bone marrow—in other parts of the body, such as the skin, they play a role in pain sensation. The researchers found that they play a role in hematopoietic stem cell mobilization.

As part of their work, the researchers were using immunofluorescent imaging to study nerve cells in the bone marrow of mice, and discovered that most of them were nociceptive nerves. That led them to wonder if these nerves played a role in hematopoietic stem cell mobilization. To find out if that might be the case, they used drugs and genetic engineering to disable them in two ways. They found that doing so had no impact on the maintenance of HSCs, but it did result in dramatically reduced hematopoietic stem cell mobilization. The researchers then tried giving the mice drugs that increased production of the neurotransmitters associated with nociceptive nerves and found that doing so increased hematopoietic stem cell mobilization, as well. Intrigued, they also gave the mice capsaicin, a component in chili pepper, and found that it also increased hematopoietic stem cell mobilization.

参考文献

Xin Gao et al. Nociceptive nerves regulate haematopoietic stem cell mobilization, Nature (2020). DOI: 10.1038/s41586-020-03057-y

Anastasia N. Tikhonova et al. Pain-sensing neurons mobilize blood stem cells from bone marrow, Nature (2020). DOI: 10.1038/d41586-020-03577-7

本文内容由振东健康网整理发布