Scientists at The Ohio State University have developed a nearly complete human brain in a dish that equals the brain maturity of a 5-week-old fetus.
The brain organoid, engineered from adult human skin cells, is the most complete human brain model yet developed, said Rene Anand, professor of biological chemistry and pharmacology at Ohio State.
The lab-grown brain, about the size of a pencil eraser, has an identifiable structure and contains 99 percent of the genes present in the human fetal brain. Such a system will enable ethical and more rapid and accurate testing of experimental drugs before the clinical trial stage and advance studies of genetic and environmental causes of central nervous system disorders.
Scientist: Most complete human brain model to date is a ‘brain changer’
Once licensed, model likely to accelerate study of Alzheimer’s, autism, more
by Emily Caldwell
https://news.osu.edu/news/2015/08/18/human-brain-model/
Scientists at The Ohio State University have developed a nearly complete human brain in a dish that equals the brain maturity of a 5-week-old fetus.
The brain organoid, engineered from adult human skin cells, is the most complete human brain model yet developed, said Rene Anand, professor of biological chemistry and pharmacology at Ohio State.
The lab-grown brain, about the size of a pencil eraser, has an identifiable structure and contains 99 percent of the genes present in the human fetal brain. Such a system will enable ethical and more rapid and accurate testing of experimental drugs before the clinical trial stage and advance studies of genetic and environmental causes of central nervous system disorders.
“It not only looks like the developing brain, its diverse cell types express nearly all genes like a brain,” Anand said. “We’ve struggled for a long time trying to solve complex brain disease problems that cause tremendous pain and suffering. The power of this brain model bodes very well for human health because it gives us better and more relevant options to test and develop therapeutics other than rodents.”
Anand reported on his lab-grown brain Tuesday (Aug. 18) at the 2015 Military Health System Research Symposium in Ft. Lauderdale, Florida.
Anand, who studies the association between nicotinic receptors and central nervous system disorders, was inspired to pursue a model of human neural biology after encountering disappointing results in a rodent study of an experimental autism drug. Taking a chance with a shoestring budget compared to other researchers doing similar projects, he added stem-cell engineering to his research program. Four years later, he had built himself a replica of the human brain.
The main thing missing in this model is a vascular system. What is there – a spinal cord, all major regions of the brain, multiple cell types, signaling circuitry and even a retina – has the potential to dramatically accelerate the pace of neuroscience research, said Anand, also a professor of neuroscience.
“In central nervous system diseases, this will enable studies of either underlying genetic susceptibility or purely environmental influences, or a combination,” he said. “Genomic science infers there are up to 600 genes that give rise to autism, but we are stuck there. Mathematical correlations and statistical methods are insufficient to in themselves identify causation. You need an experimental system – you need a human brain.”
Converting adult skin cells into pluripotent cells – immature stem cells that can be programmed to become any tissue in the body – is a rapidly developing area of science that earned the researcher who discovered the technique, Shinya Yamanaka, a Nobel Prize in 2012.
“Once a cell is in that pluripotent state, it can become any organ – if you know what to do to support it to become that organ,” Anand said. “The brain has been the holy grail because of its enormous complexity compared to any other organ. Other groups are attempting to do this as well.”
Anand’s method is proprietary and he has filed an invention disclosure with the university.
He said he used techniques to differentiate pluripotent stem cells into cells that are designed to become neural tissue, components of the central nervous system or other brain regions.
“We provide the best possible environment and conditions that replicate what’s going on in utero to support the brain,” he said of the work he completed with colleague Susan McKay, a research associate in biological chemistry and pharmacology.
High-resolution imaging of the organoid identifies functioning neurons and their signal-carrying extensions – axons and dendrites – as well as astrocytes, oligodendrocytes and microglia. The model also activates markers for cells that have the classic excitatory and inhibitory functions in the brain, and that enable chemical signals to travel throughout the structure.
It takes about 15 weeks to build a model system developed to match the 5-week-old fetal human brain. Anand and McKay have let the model continue to grow to the 12-week point, observing expected maturation changes along the way.
“If we let it go to 16 or 20 weeks, that might complete it, filling in that 1 percent of missing genes. We don’t know yet,” he said.
He and McKay have already used the platform to launch their own projects, creating brain organoid models of Alzheimer’s and Parkinson’s diseases and autism in a dish. They hope that with further development and the addition of a pumping blood supply, the model could be used for stroke therapy studies. For military purposes, the system offers a new platform for the study of Gulf War illness, traumatic brain injury and post-traumatic stress disorder.
Anand hopes his brain model could be incorporated into the Microphysiological Systems program, a platform the Defense Advanced Research Projects Agency is developing by using engineered human tissue to mimic human physiological systems.
Support for the work came from the Marci and Bill Ingram Research Fund for Autism Spectrum Disorders and the Ohio State University Wexner Medical Center Research Fund.
Anand and McKay are co-founders of a Columbus-based start-up company, NeurXstem, to commercialize the brain organoid platform, and have applied for funding from the federal Small Business Technology Transfer program to accelerate its drug discovery applications.
ほぼ完全な人間の脳、実験室で培養成功 米大学研究
AFP
http://www.afpbb.com/articles/-/3057782
極小の人間の脳をほぼ完全な形で実験室での培養に成功したとの研究結果を米大学の科学者が18日、発表した。神経系疾患の治療に大きな進歩をもたらす可能性もあるという。
米オハイオ州立大学（Ohio State University）の報告によると、小さな脳の培養に成功したのは、同大のルネ・アナンド（Rene Anand）教授。脳の成熟度は、妊娠5週の胎児に相当するという。「それは発生中の脳のように見えるだけでなく、多様な細胞型、1個の脳に匹敵するほぼ全ての遺伝子の発現もみられる」と同教授は述べている。
オハイオ州立大によると、シャーレの中でエンドウ豆ほどの大きさになったこの脳には、多種多様な細胞や脳と脊髄の主要部位の全てが含まれているが、脈管系は存在しないという。人間の皮膚細胞から培養されたこの小さな脳については、これまでに培養されたもののなかで、最も完全型に近い脳だと主張されている。
重大な研究成果は、査読学術誌に論文が投稿され、主張の内容に対して独立した評価がなされてから公表されるのが通例となっているが、アナンド教授は、18日に米フロリダ（Florida）州で開催された軍の保健関連イベントで、今回の研究成果を発表した。
同大によると、アナンド教授は、脳や神経系の疾患に対する治療法を開発する過程で、培養された脳を用いることにより、薬剤が精神に及ぼす影響をより簡単で倫理的な実験で調べることができるようになることを期待しているという。同教授と共同研究者は、脳培養システムを製品化することを目的とした新興企業をオハイオ（Ohio）州に共同で設立している。
アナンド教授は、自身の研究に関する同大の報告書の中で「この脳モデルの効力は、人間の健康に非常に明るい未来をもたらすものだ。なぜなら、治療法を試験・開発するための選択肢として、齧歯（げっし）動物を用いる以外の、より的確で関連性の高い選択肢が得られるからだ」と指摘している。
また、これは神経科学研究全般にとっても恩恵となる可能性がある。この脳を利用することで、ゲノム研究においては、現在用いられているコンピューターモデルではない実践型のアプローチを実行できるからだ。このことについては、「数学的相関法や統計的手法はそれ自体、因果関係を特定するには不十分だ。実験システム、つまり人間の脳が必要なのだ」と説明している。