New method adds missing functionality to brain organoids

July 25, 2018, New York Stem Cell Foundation
Credit: Human Brain Project

In a collaborative study between Case Western Reserve University School of Medicine, the New York Stem Cell Foundation (NYSCF) Research Institute, and George Washington University, researchers have developed a new procedure for generating miniature 3-D versions of the brain called "organoids" from human stem cells. By providing an environment for cells to interact the way they would in an actual human brain, brain organoids allow researchers to observe brain development, study disease, and test promising new drugs. The new technique, published online today in Nature Methods, creates the first organoids capable of myelination, modeling the brain's structure and function more closely than ever.

"NYSCF is committed to accelerating treatments for neurological diseases, and developing better ways for the community to use for disease research is a key part of achieving that goal," says Susan L. Solomon, NYSCF CEO. "This new method grew out of a longstanding collaboration enabled by the NYSCF community, and we are incredibly proud of the work that has resulted from this partnership."

The study was led by NYSCF—Robertson Stem Cell Investigator Alumnus Paul Tesar, Ph.D., the Dr. Donald and Ruth Weber Goodman Professor of Innovative Therapeutics and associate professor of genetics and genome sciences at Case Western Reserve University School of Medicine. The work at the NYSCF Research Institute was led by Valentina Fossati, Ph.D., NYSCF Senior Principal Investigator, who has collaborated with Dr. Tesar for years on unlocking the secrets of diseases like multiple sclerosis. Their collaboration began in 2011 through a conversation at the annual NYSCF Innovators Retreat, one of NYSCF's many endeavors to build bridges in the research community.

"When Dr. Tesar and Dr. Fossati first met at the NYSCF Innovator Retreat, the scientific sparks started to fly immediately," noted Solomon. "As this study shows, these types of collaborations are crucial for accelerating research and treatments."

Brain organoid technology has revolutionized the field by recapitulating the organization of different brain cell types, but previous organoids were missing one key ingredient: oligodendrocytes. Oligodendrocytes are brain cells that produce myelin, a substance that coats nerve fibers and helps neurons send signals. When myelin is damaged, cells cannot communicate with each other as efficiently, leading to symptoms such as numbness, loss of reflexes, uncoordinated movement, and pain. In conditions where myelin is lost, such as multiple sclerosis or spinal cord injury, oligodendrocytes are believed to play an important but poorly understood role. Incorporating oligodendrocytes capable of myelination into organoid models offers a new way to study how this process goes awry in these diseases—and to test ways to repair it.

Building on a previous protocol originally developed at the NYSCF Research Institute to generate oligodendrocytes from stem cells, the team at Case Western Reserve identified a specific combination of growth factors that could generate organoids that included oligodendrocytes. They demonstrated that myelin-enhancing drugs increased myelination by oligodendrocytes in the organoids, suggesting that these organoids could be useful in preclinical tests of drugs to repair faulty myelination. The researchers also used this method to generate organoids from stem cells of patients with Pelizaeus-Merzbacher disease—a rare but fatal genetic myelination disorder—demonstrating that the successfully modeled the characteristics of the disease. NYSCF researchers replicated the protocol independently using a different stem cell line, which was critical to demonstrate reproducibility.

"Our new method gives us a clearer picture of how brain are functioning and interacting in diseases like multiple sclerosis or Pelizaeus-Merzbacher, and it holds great promise for the development of new therapies to restore myelination," explains Dr. Tesar. "I look forward to continuing our collaboration with the NYSCF Research Institute towards better understanding and treatment of myelination disorders."

Dr. Tesar and Dr. Fossati's teams will put this new organoid protocol to work in future multiple sclerosis research, to test the effectiveness of drugs that target oligodendrocytes in an effort to stimulate myelination. Part of this work will be supported in the next three years by funding from New York State Stem Cell Science (NYSTEM). Dr. Tesar also received the 2017 NYSCF—Robertson Stem Cell Prize in recognition of his pioneering work in stem cell research for neurological diseases. His NYSCF funding was among several awards that enabled the current study.

"We're grateful for our fruitful collaboration with Dr. Tesar and thrilled that we were able to provide validation for this important technique to ensure it can be adopted by the community," says Dr. Fossati. "By filling a crucial gap in brain organoid models, we believe this new protocol will elevate research into as well as a variety of complex neurological disorders, including Alzheimer's disease and Parkinson's disease."

Explore further: Scientists 1 step closer to cell therapy for multiple sclerosis patients

More information: Mayur Madhavan et al, Induction of myelinating oligodendrocytes in human cortical spheroids, Nature Methods (2018). DOI: 10.1038/s41592-018-0081-4

Related Stories

Scientists 1 step closer to cell therapy for multiple sclerosis patients

July 24, 2014
Scientists at The New York Stem Cell Foundation (NYSCF) Research Institute are one step closer to creating a viable cell replacement therapy for multiple sclerosis from a patient's own cells.

Team announces robust, high-throughput protocol for deriving microglia from human stem cells

May 18, 2017
Scientists from the New York Stem Cell Foundation (NYSCF) Research Institute have developed a robust, efficient method for deriving microglia, the immune cells of the brain, from human stem cells. Microglia are increasingly ...

Scientists develop 3-D stem cell culture technique to better understand Alzheimer's disease

April 2, 2013
A team of researchers at The New York Stem Cell Foundation Research Institute led by Scott Noggle, PhD, Director of the NYSCF Laboratory and the NYSCF – Charles Evans Senior Research Fellow for Alzheimer's Disease, and ...

NYSCF and BBDF announce the availability of stem cell lines for research

October 4, 2017
The New York Stem Cell Foundation (NYSCF) and Beyond Batten Disease Foundation (BBDF) today announce the availability of a unique and comprehensive collection of juvenile Batten (CLN3) disease induced pluripotent stem (iPS) ...

Recommended for you

Precision neuroengineering enables reproduction of complex brain-like functions in vitro

November 14, 2018
One of the most important and surprising traits of the brain is its ability to dynamically reconfigure the connections to process and respond properly to stimuli. Researchers from Tohoku University (Sendai, Japan) and the ...

New brain imaging research shows that when we expect something to hurt it does, even if the stimulus isn't so painful

November 14, 2018
Expect a shot to hurt and it probably will, even if the needle poke isn't really so painful. Brace for a second shot and you'll likely flinch again, even though—second time around—you should know better.

New clues to the origin and progression of multiple sclerosis

November 13, 2018
Mapping of a certain group of cells, known as oligodendrocytes, in the central nervous system of a mouse model of multiple sclerosis (MS), shows that they might have a significant role in the development of the disease. The ...

Mutations, CRISPR, and the biology behind movement disorders

November 12, 2018
Scientists at the RIKEN Center for Brain Science (CBS) in Japan have discovered how mutations related to a group of movement disorders produce their effects. Published in Proceedings of the National Academy of Sciences, the ...

In live brain function, researchers are finally seeing red

November 12, 2018
For years, green has been the most reliable hue for live brain imaging, but after using a new high-throughput screening method, researchers at the John B. Pierce Laboratory and the Yale School of Medicine, together with collaborators ...

Concussion tied to suicide risk

November 12, 2018
(HealthDay)—People who have experienced either a concussion or a mild traumatic brain injury are twice as likely to commit suicide than others, a new review suggests.


Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.