Molecule guides stem cells to damaged brain tissue

分子将干细胞引导至受损的脑组织

Researchers altered a molecule that is naturally produced by the body to safely guide stem cells to damaged brain tissue.

研究人员改变了人体天然产生的分子，以安全地将干细胞引导至受损的脑组织。

Mice with a fatal brain disease had delayed onset of symptoms and improved survival when given the new molecule and neural stem cells.

当使用新的分子和神经干细胞时，患有致命性脑病的小鼠可延迟症状发作并提高生存率。

With further development, the approach may have applications for human disease.

随着进一步的发展，该方法可能会应用于人类疾病。

Neural stem cells maturing into brain cells called astrocytes (yellow). Sanford Burnham Prebys Medical Discovery Institute

神经干细胞成熟为脑细胞，称为星形胶质细胞（黄色）。桑福德·伯纳姆·普雷比斯医学发现研究所

Stem cells are part of the body’s repair system. They have the potential to replace specialized cells—such as muscle cells, blood cells, and brain cells—that have been damaged by injury or disease.

干细胞是人体修复系统的一部分。它们有潜力替代因损伤或疾病而受损的特殊细胞，例如肌肉细胞，血细胞和脑细胞。

The amount of repair that stem cells do in the adult body is limited. Researchers have been looking for ways to draw more stem cells to injured areas and focus their work. Harnessing the body’s healing mechanisms in this way is called regenerative medicine.

干细胞在成年体内所做的修复数量有限。研究人员一直在寻找将更多的干细胞吸引到受伤部位并集中精力工作的方法。通过这种方式利用人体的康复机制，称为再生医学。

To attract stem cells to injured tissues, the body naturally releases chemicals called chemokines. But chemokines also cause inflammation, and long-term inflammation in the brain and body can cause more harm than good. Therefore, it hasn’t been considered safe to use natural chemokines for regenerative medicine.

为了吸引干细胞至受伤的组织，人体自然释放出称为趋化因子的化学物质。但是趋化因子也会引起炎症，大脑和身体的长期炎症可能造成弊大于利。因此，将天然趋化因子用于再生医学并不安全。

A research team led by Dr. Evan Snyder from the Sanford Burnham Prebys Medical Discovery Institute tested whether they could engineer a natural chemokine to attract stem cells without causing inflammation. They altered a chemokine called CXCL12, which can draw neural stem cells to sites of injury or disease in the brain and central nervous system. CXCL12 binds to a receptor called CXCR4 on the surface of these stem cells.

由桑福德·伯纳姆·普雷姆斯医学发现研究所的埃文·斯奈德（Evan Snyder）博士领导的研究小组测试了它们是否可以工程化天然趋化因子以吸引干细胞而不引起炎症。他们改变了一种称为CXCL12的趋化因子，它可以将神经干细胞吸引到大脑和中枢神经系统的损伤或疾病部位。 CXCL12与这些干细胞表面上称为CXCR4的受体结合。

When activated, CXCR4 can signal different reactions within the cells. Using computational methods, the researchers optimized the part of CXCL12 that initially binds CXCR4. They then replaced the portion that triggers CXCR4 to boost inflammation. The work was funded in part by NIH’s National Institute of General Medical Sciences (NIGMS). Results were published on November 20, 2020,in Proceedings of the National Academy of Sciences.

激活后，CXCR4可以发出细胞内不同反应的信号。研究人员使用计算方法优化了最初绑定CXCR4的CXCL12部分。然后，他们替换了触发CXCR4增强炎症的部分。这项工作部分由美国国立卫生研究院的国立普通医学科学研究所（NIGMS）资助。结果于2020年11月20日发布在美国国家科学院院刊上。

After testing different versions of the molecule in laboratory experiments, the team focused on one called SDV1a. SDV1a strongly encouraged neural stem cells to migrate towards its signal without activating genes associated with inflammation. Instead, it activated genes involved in tissue repair.

在实验室实验中测试了该分子的不同版本之后，该团队专注于开发一种名为SDV1a的分子。 SDV1a强烈鼓励神经干细胞向其信号迁移而不激活与炎症相关的基因。相反，它激活了参与组织修复的基因。

The team next tested their new molecule in the brains of healthy mice. When they injected SDV1a into one side of the brain and neural stem cells into the other, the cells migrated to the side with SDV1a. Both SDV1a and the stem cells remained active in the brain for weeks. The mice showed no inflammation or other side effects from treatment.

接下来，研究小组在健康小鼠的大脑中测试了他们的新分子。当他们将SDV1a注射到大脑的一侧，而将神经干细胞注射到另一侧时，这些细胞就会与SDV1a一起迁移到一侧。 SDV1a和干细胞在大脑中都保持活跃数周。小鼠从治疗中未显示出炎症或其他副作用。

Finally, the researchers gave the combination of SDV1a and neural stem cells to mice with a deadly degenerative brain disorder. SDV1a was injected into the brain’s cortex, and stem cells were implanted into ventricles—brain cavities filled with cerebrospinal fluid.

最后，研究人员将SDV1a和神经干细胞的组合给予患有致命性变性脑疾病的小鼠。将SDV1a注入大脑皮层，然后将干细胞植入脑室，脑室中充满了脑脊液。

The stem cells spread throughout the brain and produced new neurons. Mice that received the treatment had slower onset of disease symptoms and lived longer.

干细胞遍布整个大脑并产生新的神经元。接受治疗的小鼠疾病症状发作较慢，寿命更长。

“The ability to instruct a stem cell where to go in the body or to a particular region of a given organ is the Holy Grail for regenerative medicine,” Snyder says. “Now, for the first time ever, we can direct a stem cell to a desired location and focus its therapeutic impact.”

斯奈德说：“指示干细胞进入人体或特定器官特定部位的能力是再生医学的圣杯。” “现在，有史以来第一次，我们可以将干细胞定向到所需位置并集中其治疗作用。”

The team is now testing their approach in a mouse model of amyotrophic lateral sclerosis (ALS). Similar strategies may help improve stem cell therapy for spinal cord injury and stroke, as well as boost repair in other parts of the body.

该团队现在正在肌萎缩性侧索硬化症（ALS）小鼠模型中测试他们的方法。类似的策略可能有助于改善针对脊髓损伤和中风的干细胞疗法，以及促进身体其他部位的修复。

—by Sharon Reynolds

—莎朗·雷诺兹（Sharon Reynolds）

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 来源于：nih