Growing human brain cells in the labOctober 10, 2017
San Francisco, CA--Li Gan, PhD, wants to find treatments to help patients with Alzheimer's disease. Like most researchers, she's hit a few major roadblocks.
When researchers like Gan find potential new drugs, they must be tested on human cells to confirm they can benefit patients. Historically, these tests have been conducted in cancer cells, which often don't match the biology of human brain cells.
"The problem is that brain cells from actual people can't survive in a dish, so we need to engineer human cells in the lab," explained Gan, senior investigator at the Gladstone Institutes. "But, that's not as simple as it may sound."
Many scientists use induced pluripotent stem cells (iPSCs) to address this issue. IPSCs are made by reprogramming skin cells to become stem cells, which can then be transformed into any type of cell in the body. Gan uses iPSCs to produce brain cells, such as neurons or glial cells, because they are relevant to neurodegenerative disease.
Human brain cells derived from iPSCs offer great potential for drug screening. Yet, the process for producing them can be complicated, expensive, and highly variable. Many of the current methods produce cells that are heterogeneous, or different from one another, and this can lead to inconsistent results in drug screening. In addition, producing a large number of cells is very costly, so it's difficult to scale up for big experiments.
To overcome these constraints, Michael Ward, MD, PhD, had an idea.
A New Technique Is Born
"I came across a new method to produce iPSCs that was developed at Stanford," said Ward, a former postdoctoral scholar in Gan's lab who is now an investigator at the National Institutes of Health. "I thought that if we could find a way to simplify and better control that approach, we might be able to improve the way we engineer human brain cells in the lab."
Ward and his colleague Chao Wang, PhD, discovered a way to manipulate the genetic makeup of cells to produce thousands of neurons from a single iPSC. This meant that every engineered brain cell was now identical.
"I was truly motivated by our initial results," said Gan, who is also a professor of neurology at UC San Francisco. "I had observed too much variability using the traditional method, which made reproducing experiments quite problematic. So, the ability to produce homogeneous human brain cells was very exciting."
The team further improved the technique to create a simplified, two-step process. This allows scientists to precisely control how many brain cells they produce and makes it easier to replicate their results from one experiment to the next.
Their technique also greatly accelerates the process. While it would normally take several months to produce brain cells, Gan and her team can now engineer large quantities of them within 1 or 2 weeks, and have functionally active neurons within 1 month.
The researchers realized this new approach had tremendous potential to screen drugs and to study disease mechanisms. To prove it, they tested it on their own research.
They applied their technique to produce human neurons by using iPSCs. Then, they developed a drug discovery platform and screened 1,280 compounds. Their goal is to identify the compounds that could lower levels of the protein tau in the brain, which is considered one of the most promising approaches in Alzheimer's research and could potentially lead to new drugs to treat the disease.
"We showed that we can engineer large quantities of human brain cells that are all the same, while also significantly reducing the costs," said Wang, Gladstone postdoctoral scholar. "This means our technology can easily be scaled up and can essentially be used to screen millions of compounds."
A Powerful Tool for the Entire Scientific Community
"We have developed a cost-effective technology to produce large quantities of human brain cells in two simple steps," summarized Gan. "By surmounting major challenges in human neuron-based drug discovery, we believe this technique will be adopted widely in both basic science and industry."
Word of this useful new technology has already spread, and people from different scientific sectors have come knocking on Gan's door to learn about it. Her team has shared the new method with scores of academic colleagues, some of whom had no experience with cell culture. So far, they all successfully repeated the two-step process to produce their own cells and facilitate scientific discoveries.
Details of this new technique were also published on October 10, 2017, in the scientific journal Stem Cell Reports.
With some of the roadblocks out of the way, Gan hopes more discoveries will soon help the millions who suffer from Alzheimer's disease.
To ensure our work does the greatest good, the Gladstone Institutes focuses on conditions with profound medical, economic, and social impact--unsolved diseases. Gladstone is an independent, nonprofit life science research organization that uses visionary science and technology to overcome disease. It has an academic affiliation with the University of California, San Francisco.
Related Stem Cells Articles:
Researchers have identified a protein that must be present in order for mammary stem cells to perform their normal functions.
Researchers at Boston Children's Hospital have, for the first time, generated blood-forming stem cells in the lab using pluripotent stem cells, which can make virtually every cell type in the body.
Researchers have developed a new approach for growing and studying cells they hope one day will lead to curing lung diseases such as cystic fibrosis through 'personalized medicine.'
Generating mature and viable heart muscle cells from human or other animal stem cells has proven difficult for biologists.
DNA mutations in bone cells that support blood development can drive leukemia formation in nearby blood stem cells.
With age, the chromosomes of our cardiac stem cells compress as they move into a state of safe, semiretirement.
A team of researchers from the Medical University of South Carolina and elsewhere has found a better way to purify liver cells made from induced pluripotent stem cells.
International stem cell scientists, co-led in Canada by Dr. John Dick and in the Netherlands by Dr.
Signaling a potential new approach to treating diabetes, researchers at Washington University School of Medicine in St.
In a new Cell Reports paper, a team led by John P.
Related Stem Cells Reading:
Stem Cell Therapy: A Rising Tide: How Stem Cells Are Disrupting Medicine and Transforming Lives
by Neil H Riordan (Author)
Stem cells are the repair cells of your body. When there aren’t enough of them, or they aren’t working properly, chronic diseases can manifest and persist. From industry leaders, sport stars, and Hollywood icons to thousands of everyday, ordinary people, stem cell therapy has helped when standard medicine failed. Many of them had lost hope. These are their stories.
Neil H Riordan, author of MSC: Clinical Evidence Leading Medicine’s Next Frontier, the definitive textbook on clinical stem cell therapy, brings you an easy-to-read book about how and why stem cells work,... View Details
Stem Cells: An Insider's Guide
by Paul Knoepfler (Author)
Stem Cells: An Insider's Guide is an exciting new book that takes readers inside the world of stem cells guided by international stem cell expert, Dr. Paul Knoepfler. Stem cells are catalyzing a revolution in medicine. The book also tackles the exciting and hotly debated area of stem cell treatments that are capturing the public's imagination. In the future they may also transform how we age and reproduce. However, there are serious risks and ethical challenges, too. The author's goal with this insider's guide is to give readers the information needed to distinguish between the... View Details
Stem Cell Revolution: Discover 26 Disruptive Technological Advances to Stem Cell Activation
by Joseph Christiano (Author)
Addressing chronic back pain, diabetes, joint replacements, osteoarthritis, neurological issues, and more, Joseph “Dr. Joe” Christiano reveals
how this cutting-edge therapy can rapidly replace damaged cells in the body with no side effects or allergic reactions.
If you have been disappointed by ineffective treatments, the answer to improving your health may be in your stem cells. Dr. Joe explains
how adult stem cell therapy and activators are two of the new technologies in regenerative medicine that will be game changers in medical history.
... View Details
Stem Cells For Dummies
by Lawrence S.B. Goldstein (Author), Meg Schneider (Author)
The first authoritative yet accessible guide to this controversial topic
Stem Cell Research For Dummies offers a balanced, plain-English look at this politically charged topic, cutting away the hype and presenting the facts clearly for you, free from debate. It explains what stem cells are and what they do, the legalities of harvesting them and using them in research, the latest research findings from the U.S. and abroad, and the prospects for medical stem cell therapies in the short and long term.Explains the differences between adult stem cells and embryonic/umbilical... View Details
Stem Cells: Promise and Reality
by Lygia V Pereira (Author)
Stem Cells: Promises and Reality will tell you everything you have always wanted to know about stem cells, but could not understand the field from elsewhere. Stem cells are the great therapeutic promise of the century, and this evolving field of research and medicine brings with it many legal, ethical and psychological issues that must be discussed by society as a whole. Written so as to be accessible to general readers as well as specialists, this book explains what stem cells are, and the different aspects of stem cell research and applications. The book will enable the reader to understand... View Details
The Stem Cell Revolution
by Mark Berman MD (Author), Elliot Lander MD (Contributor)
The book describes the journey into the growing arena of clinical stem cell therapy by highlighting not only the road that brought a team of physicians together but also real stories from a number of their patients that were given their health back through the magic of stem cell therapy. Your fat is loaded with stem cells that can be used now to treat and reverse a large number of inflammatory and degenerative conditions. Most people have no idea that these magical cells actually exist right within our bodies. They think that they must wait until Big Pharma or a university PhD manufactures... View Details
Stem Cells Are Everywhere
by Irv Weissman MD (Author)
An engaging introduction to stem cells for young scientists
How do you heal when you cut your skin or break a bone? How does your body keep making new blood or brain cells, or even second teeth? How does a plant keep growing larger? The answers lie in stem cells, which are found in every growing plant and animal. Keeping the subject simple enough for young readers, a pioneer of stem cell research explains cells, tissues, normal growth, what can go wrong, and how to fix it. View Details
Stem Cells: A Short Course
by Rob Burgess (Author)
Stem Cells: A Short Course is a comprehensive text for students delving into the rapidly evolving discipline of stem cell research. Comprised of eight chapters, the text addresses all of the major facets and disciplines related to stem cell biology and research. A brief history of stem cell research serves as an introduction, followed by coverage of stem cell fundamentals; chapters then explore embryonic and fetal amniotic stem cells, adult stem cells, nuclear reprogramming, and cancer stem cells. The book concludes with chapters on stem cell applications, including the role of stem... View Details
Stem Cells: A Very Short Introduction
by Jonathan Slack (Author)
Embryonic stem cells have been hot-button topics in recent years, generating intense public interest as well as much confusion and misinformation. In this Very Short Introduction, leading authority Jonathan Slack offers a clear and informative overview of stem cells--what they are, what scientists do with them, what stem cell therapies are available today, and how they might be used in the future. Slack explains the difference between embryonic stem cells, which exist only in laboratory cultures, and tissue-specific stem cells, which exist in our bodies, and he discusses how... View Details
STEM CELLS : VERY SHORT INTRODUCTION
by Jonathan Slack (Author)
Embryonic stem cells have been hot button topics in recent years generating intense public interest as well as much confusion and misinformation In thisVery Short Introduction leading authority Jonathan Slack offers a clear and informative overview of stem cells what they are what scientists do with them what stem cell therapies are available today and how they might be used in the future Slack explains the difference between embryonic stem cells which exist only in laboratory cultures and tissue specific stem cells which exist in our bodies and he discusses how embryonic stem cells may be... View Details