Whatever you do, don’t call them “mini-brains,” say University of Utah Health scientists. 不管, the seed-sized organoids—which are grown in the lab from human cells—provide insights into the brain and uncover differences that may contribute to autism in some people.
“We used to think it would be too difficult to model the organization of cells in the brain,” says Alex Shcheglovitov博士他是大发娱乐神经生物学助理教授. “但是这些类器官是自我组织的. 几个月内, we see layers of cells that are reminiscent of the cerebral cortex in the human brain.”
The research describing the organoids and their potential for understanding neural diseases publishes in 自然通讯 on Oct 6 with Shcheglovitov as senior author and Yueqi Wang, 博士学位, 一个前研究生在他的实验室里, 作为第一作者. They carried out the research with postdoctoral scientist Simone Chiola, 博士学位, 以及犹他大学的其他合作者, 哈佛大学, 米兰大学, 和蒙大拿州立大学.
“这些类器官可以自我组织. 几个月内, we see layers of cells that are reminiscent of the cerebral cortex in the human brain.”
调查自闭症
Having the ability to model aspects of the brain in this way gives scientists a glimpse into the inner workings of a living organ that is otherwise nearly impossible to access. 既然类器官是在培养皿中生长的, they can be tested experimentally in ways that a brain cannot.
Shcheglovitov’s team used this approach to investigate effects of a genetic abnormality associated with autism spectrum disorder and human brain development. They found that organoids engineered to have lower levels of the gene, called SHANK3，有着鲜明的特点。.
Even though the autism organoid model appeared normal, some cells did not function properly:
- Neurons were hyperactive, firing more often in response to stimuli,
- Other signs indicated neurons may not efficiently pass along signals to other neurons,
- Specific molecular pathways that cause cells to adhere to one another were disrupted.
These findings are helping to uncover the cellular and molecular causes of symptoms associated with autism, 作者说. They also demonstrate that the lab-grown organoids will be valuable for gaining a better understanding of the brain, 它是如何发展的, 以及疾病期间出了什么问题.
“一个关键的应用是使用大脑类器官, derived from the genetic material of each individual patient, to test drugs or other interventions to treat disorders in a personalized manner,Jan Kubanek说, 博士学位, a co-author on the study and an assistant professor of biomedical engineering at the U. “This would truly realize the potential of personalized medicine.”
建立一个更好的大脑模型
Scientists have long searched for suitable models for the human brain. 实验室培养的类器官并不新鲜, but previous versions did not develop in a reproduceable way, 使实验难以解释.
To create an improved model, Shcheglovitov’s team took cues from how the brain develops normally. The researchers prompted human stem cells to become neuroepithelial cells, a specific stem cell type that forms self-organized structures, 叫做神经玫瑰花, 在盘子里. 几个月过去了, these structures coalesced into spheres and increased in size and complexity at a rate similar to the developing brain in a growing fetus.
在实验室待了五个月之后, the organoids were reminiscent of “one wrinkle of a human brain” at 15 to 19 weeks post-conception, Shcheglovitov说. The structures contained an array of neural and other cell types found in the cerebral cortex, 大脑中与语言有关的最外层, 情感, 推理, 以及其他高层次的心理过程.
就像人类胚胎一样, 类器官以一种可预测的方式自我组织, forming neural networks that pulsated with oscillatory electrical rhythms and generated diverse electrical signals characteristic of a variety of different kinds of mature brain cells.
“These organoids had patterns of electrophysiological activity that resembled electrophysiological rhythms of the brain. 我没想到会这样，”库班尼克说. “This new approach models functional brain networks of the human nervous tissue.”
Shcheglovitov解释说，这些类器官, which more reliably reflect intricate structures in the cortex, will allow scientists to study how specific types of cells in the brain arise and work together to perform more complex functions.
“We’re beginning to understand how complex neural structures in the human brain arise from simple progenitors,王说. “And we’re able to measure disease-related phenotypes using 3D organoids that are derived from stem cells containing genetic mutations.”
他补充说，使用类器官, researchers will be able to better investigate what happens at the earliest stages of neurological conditions, 在症状出现之前.
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访问 UBrain浏览器 to visualize the cells and electrical responses detected in organoids.
Support for the work came from the National Institutes of Health, 大脑研究基金会, 脑与行为研究基金会, 白厅的基础, 犹他大学神经科学计划, 犹他大学基因组计划倡议.