Researchers created a new high-throughput tool to hunt for therapies that remyelinate the nervous system.
研究人造了一,新的高通量工具,找使神系之髓鞘(包裹每神胞的膜)再生的法。
If the nervous system is an information highway similar to the internet, the myelin sheath is the signal booster that helps the Wi-Fi quickly and consistently reach every room in a home.
倘若神系是一似路的信息高速公路,那髓鞘就是助Wi-Fi,快速、一致地到家中,每房的信增器。
Just as a patchy internet connection disrupts the flow of information from router to electronic device, demyelination slows or halts nerve impulses between the central nervous system (CNS) and the rest of the body. Cells that are responsible for making myelin are called oligodendrocytes.
正如同不定的路接,路由器到子的信息流。髓鞘也慢或中止,中神系(CNS)身其他部位之的神。生髓鞘(包裹神的脂肪物)的胞,被少突胞。
In a healthy CNS, oligodendrocyte precursor cells (OPCs) migrate to sites of demyelination and produce oligodendrocytes. However, this process is disrupted in demyelination disorders such as multiple sclerosis (MS).
在健康的中神系中,少突胞前身胞(OPCs)移到髓鞘部位,生少突胞。不,在如多性硬化症(MS)等,髓鞘疾病中,此程遭到干。
In MS, a patient’s immune system mistakenly attacks the myelin sheath. Inflammation damages the neurons left vulnerable by demyelination, and causes a range of symptoms, including vision loss, muscle weakness and dysfunction, and sensory changes.
在多性硬化症中,患者免疫系地攻髓鞘。炎因髓鞘脆弱的神元,引起包括力失、肌肉力能障及知改等,一系列症。
Current MS therapies target the immune system to slow disease progression, but scientists seek a more direct therapeutic approach.
目前,多性硬化症法定免疫系,疾病展。不,科家求一更直接的治方法。
“Just by stopping the immune system, you can’t recover the myelin that’s degraded,” explained Xitiz Chamling, a neuroscientist at Johns Hopkins University. “There is a huge interest in this field to re-establish myelin, which is called remyelination.”
美翰霍普金斯大神科家,Xitiz Chamling解:「藉由中止免疫系,法元降解的髓鞘。在被髓鞘再生之重建髓鞘的域中,有一件令人感趣的事。」
This interest stems from the potential to cure or reverse the disease with treatments that promote myelination by oligodendrocytes.
此令人感趣之事源自,以促由少突胞之髓鞘形成的治法,治或逆疾病的力。
1. 人少突胞(色)被星形胞包,全部源自Chamling工程理之三重信息的多能胞(hPSC)系。
A human oligodendrocyte (green) surrounded by astrocytes, all derived from Chamling’s engineered triple reporter pluripotent stem cell (hPSC) line.
Chamling develops tools that scientists can use to search for remyelination therapeutics. In their latest work published in iScience, Chamling’s team created a stem cell-based high-throughput screening platform to identify small molecules that promote remyelination, finding old and new drug candidates to treat MS.
Chamling了多,科家能用找,髓鞘再生法的工具。在他最近表於,Cell Press新放之存取期刊《iScience》表的研究中,Chamling的造了一,以胞基之高通量平台,促髓鞘再生的小分子,以找治多性硬化症的新、候物。
The researchers built the platform by genetically engineering human pluripotent stem cells (hPSCs) with three reporter genes. They used CRISPR-Cas9 to introduce genetic instructions that tell the cells to create protein tags in specific contexts, allowing the researchers to visually monitor and physically capture the stem cells that differentiated into OPCs and oligodendrocytes.
此些研究人藉由工程改造,具有三重信息基因的人多能胞(hPSC),建了上述平台。他使用了,CRISPR-Cas9 (Cas9(CRISPR associated protein 9:是一在某些菌DNA病毒之免疫防中,起至重要作用的蛋白)群聚、律性隔的短文(CRISPR:Clustered Regularly Interspaced Short Palindromic Repeat)
)入,告此些胞,在特定境下,生蛋白的指令。使研究人得以上上捕,分化成少突胞前身胞(OPC)及少突胞的胞。
Chamling’s team then screened thousands of therapeutics with the potential to promote OPC maturation. “Finding the right drug or therapeutic tool to push those OPCs to mature into oligodendrocytes and help them form myelin is really interesting,” said Chamling.
之後,Chamling的了,千具有促OPC成熟力的法。Chamling宣:「找物或治工具,推那些OPC,成熟少突胞,及助它形成髓鞘,是非常令人感趣的。」
His work is a unique approach among other established high-throughput screening platforms in the hunt for remyelination therapeutics.
在找髓鞘再生法上,他的研究是其他建立之高通量平台中的一特方法。
“All of the past assays for the screening component have been in rodent systems, both primary and pluripotent stem cell-derived. The challenges of the human system are numerous, and this group really put a lot of effort into tackling each of those challenges,” said Paul Tesar, a developmental biologist from Case Western Reserve University School of Medicine and co-founder of Convelo Therapeutics, who was not involved in the study. “We were really excited when this paper came out, because it provided the first scalable ability to screen in human oligodendrocyte progenitor cells.”
未涉及研究之生物科技公司Convelo Therapeutics共同始人,自美斯西大院的育生物家,Paul Tesar宣:「去所有成分的,一直是使用包括原生胞及多能胞衍生的物。人的挑有很多,因此付出了很多努力,每一那些挑。此文表,我非常。因它提供了,第一模可改的能耐,人少突胞的前身胞。」
Chamling’s research team used their platform to identify new molecules that promote myelination and corroborated many hits that other researchers such as Tesar previously identified with rodent-derived stem cell screening platforms.
Chamling的研究利用了他的平台,促髓鞘形成的新分子,且了如Tesar等,其他研究人之前,以源自物胞之平台,的多成果。
This solidified the validity of this new hPSC-derived system and opened opportunities to investigate human-specific pathways on a large scale.
固了,源自hPSC之新方法的有效性,了大模查研究人特性途的多。
“I think it's likely that there are human-specific factors that we could go after,” Tesar explained. “Whether or not they're better or worse than the ones that are conserved across species is a separate question, but I think this does open up a new ability to explore human oligodendrocyte development, which is exciting.”
Tesar解:「我,有多我能追之人特有的因素。於各物中,它是否保存的更好或更差,是一不同的。不我,了,探索人少突胞育的新能耐,是令人振的。」
址:https://www.the-scientist.com/news/searching-for-a-direct-route-to-multiple-sclerosis-treatment-71218
翻:
文章定位: