从人胚胎干细胞得到的神经元可以适应并调节鼠类已有的神经网络

tinatina

PNAS（11月21日）发表J.P. Weick et al., 文章，从人胚胎干细胞得到的神经元既可以发出，也可以介绍电信号。
' b* ?( {- k% R. U2 g0 cNeurons made from human embryonic stem cells (hESCs) can both send and receive nerve impulses when transplanted into the mouse brain, according to a report published today (November 21) in Proceedings of the National Academy of Sciences. The discovery provides some of the strongest evidence that hESC-derived neurons, which could be used to treat a variety of neurological disorders such as epilepsy, stroke, and Parkinson’s disease, can fully integrate and behave like regular neurons when transplanted into the brain.
6 K( G' z5 N9 k6 x6 l+ m8 Z$ G4 t) H6 S5 S: t2 d( R. {: ?
“We’ve known for decades that [transplanted neurons] can receive information,” said Jason Weick of the University of Wisconsin, who was the lead author on the study. Once the cells are in the brain, he explained, their electrical activity can be simply recorded. The missing part of the puzzle was, he said, “Can the cells output to the brain?”2 V! Z' q0 S8 z& L1 `
4 `$ L7 H  D1 x. I1 G0 N$ n
To find out, “they used some very clever tricks to control the activity of the [transplanted] cells,” said Hongjun Song of the Johns Hopkins University, who was not involved in the study.( @7 t' P, o7 u. n% L9 ^

/ c0 N' ]" F  n0 r) d/ kThose clever tricks employed the powerful techniques of optogenetics. Specifically, the researchers expressed light-sensitive ion channels from algae in hESC-derived neurons such that they incorporated into the membrane. In response to light, these channels sent a flood of ions surging into the cell triggering it to fire an action potential. (Watch a video on optogenetics.)
' I7 m4 F( r, D0 j& g+ Z# e# t0 o$ P& q  v7 c5 K, I' b
When the engineered neurons were co-cultured with mouse neurons or transplanted into mouse brains that were later prepared as slices, the team could simply flip on a light—an LED linked to a fiber optic cable placed a few millimeters from the cells—and look for activity from the mouse neurons. Sure enough, the mouse cells were receiving impulses from the hESC-derived neurons, and conversely, the human cells could also receive impulses from the mouse neurons.8 q. F9 m; `- ~/ o  w* Q

* y) |7 Y6 P4 E0 o# N“[It is] the most convincing demonstration thus far of functional integration of human embryonic stem cell-derived neurons into existing neural networks,” said Steve Goldman of the University of Rochester Medical Center, who was not involved in the study. Indeed, echoed Song, “For the first time they were able to show that the cells can modulate the existing neurocircuitry.”+ T+ B% F/ o8 ^. e; a
# ?" B4 }, F/ W
Researchers have shown previously that hESC-derived neurons transplanted into rat brains could modulate the animals’ behavior. Although this suggested functional integration, Song pointed out, “behavior doesn’t have enough resolution to tell you what exactly is happening.” The new study provides more definitive proof." o4 }8 {) O) C' i4 T/ t" }! z
$ e4 [' k" H0 l& f( y
That said, Goldman thinks that showing how these cells function in a living animal will be an important next step. “Slice preparations are not the same as looking at the live brain,” he said.
$ I! M3 S3 M* O, p9 R2 n( `
8 U4 i( O1 X: ?/ |, x: IAssuming the results hold true in live animals, the optogenetic approach could be used to accurately examine how the cells find their home and their partners, said Song. Furthermore, rather than simply being a tool for research, light-responsive neurons could be used to treat patients.
  _1 q2 \# G9 {. j  b% M( u9 y3 |4 {' b
“We’re moving into the realm of treating animal models, at least, with cell replacement,” said Weick, “and at the same time being able to control the output of the transplant.”
/ N& T; h: d1 M2 ?; N4 T2 E7 x+ q! U$ d# b
Longer term, Weick envisages the same paradigm applying to humans. “Let’s say you are having a particularly bad day, your Parkinson’s symptoms are awful, but you’ve received this transplant [of cells] and you have an implantable light stimulation device,” he said. In that case, “you can simply ratchet-up the stimulation.”
8 Q! `5 ^) T9 y3 f# J8 S& ~* k% a2 |$ N, f1 S; |- v$ U
2 R: c' s0 Z0 ~" Z* x) f
J.P. Weick et al., “Human embryonic stem cell-derived neurons adopt and regulate the activity of an established neural network,” Proceedings of the National Academy of Sciences, www.pnas.org/cgi/doi/10.1073/pnas.1108487108, 2011.7 K- y. A  G5 T! D0 K

. l! P7 C$ G$ z; a* ]+ b2 h

细胞海洋

生物通报道：来自威斯康辛大学麦迪逊分校的研究人员发表了题为“Human embryonic stem cell-derived neurons adopt and regulate the activity of an established neural network”的文章，证明了来源于胚胎干细胞人类的神经元能够调节宿主神经细胞网络行为，这朝着成功的神经疾病细胞移植疗法迈出的关键一步。相关成果公布在《美国国家科学院院刊》（PNAS）杂志上。
% O5 y% J3 T% G. \+ T  E; [+ W以前已有研究证明，从干细胞中提取出的人类神经元移植进鼠大脑后，其能与鼠大脑中的主神经元整合在一起并接收主神经元发出的信号。但科学家们一直没有证明这种移植细胞能成功地朝主神经元发出信号并调控主神经元的活动。( W4 U) J2 y$ h" n  a
在这篇文章中，研究人员将被光活化后的来自人类胚胎干细胞（hESCs）的神经元移植有各种神经性退化疾病的小鼠大脑，用于分析在体外及在小鼠大脑中的移植的人类细胞整合到小鼠神经元的能力。
4 ]& ^! h# G+ ?" P4 ?结果发现来自人类胚胎干细胞的神经元可以在活小鼠的大脑中功能整合起，这可能对于研发针对帕金森病、阿兹海默病、中风和癫痫的新治疗方法具有重要意义，文章通讯作者Jason P. Weicka表示，这令人不可思议，现在从本质上说，我们能够为特定的疾病定制神经元了。
6 f: L3 B8 d0 g! O( O/ H. E研究人员把这些人类细胞与小鼠神经元细胞共同培养，显示出了同步的神经活动。尽管来自人类胚胎干细胞的神经元通常并不显示出这种行为，这些人类细胞逐渐在与小鼠神经元的生长过程中出现了冲动活动。此外，用光刺激这些人类神经元能引发小鼠神经元的冲动行为，这表明了人类与小鼠神经元的互动。光刺激也引发了移植来自人类胚胎干细胞的神经元的小鼠大脑切片的小鼠神经元的响应，这提示移植的神经元可以通过功能整合参与到神经元网络并且控制神经元网络的活动。 ) S8 R/ L/ W- n+ n  Z( T  M/ q
来自美国约翰霍普金斯大学的宋红军表示，“这十分令人激动”，“你能够放入小量的细胞并得到巨大的效果”，这项技术可提供一个平台，让科学家们研究诸如哪类主神经元会做出反应等问题。研究人员现正在将这些光能激活的神经元移植入罹患各种神经退化性疾病的老鼠大脑中。, z4 m: D7 d- j1 ?& Z+ d$ L- H
原文摘要：
4 h9 j9 V. c% A; \# m% P5 o* @% y" p  V5 X" m( ?
Human embryonic stem cell-derived neurons adopt and regulate the activity of an established neural network- z4 S" W5 ]. g4 P% u, d

/ V' }+ G2 v3 @2 `+ uWhether hESC-derived neurons can fully integrate with and functionally regulate an existing neural network remains unknown. Here, we demonstrate that hESC-derived neurons receive unitary postsynaptic currents both in vitro and in vivo and adopt the rhythmic firing behavior of mouse cortical networks via synaptic integration. Optical stimulation of hESC-derived neurons expressing Channelrhodopsin-2 elicited both inhibitory and excitatory postsynaptic currents and triggered network bursting in mouse neurons. Furthermore, light stimulation of hESC-derived neurons transplanted to the hippocampus of adult mice triggered postsynaptic currents in host pyramidal neurons in acute slice preparations. Thus, hESC-derived neurons can participate in and modulate neural network activity through functional synaptic integration, suggesting they are capable of contributing to neural network information processing both in vitro and in vivo.