Welcome!

News Feed Item

First stem cell study of bipolar disorder yields promising results, U-M & Prechter Fund scientists say

Stem cell model shows nerve cells develop, behave & respond to lithium differently - opening doors to potential new treatments

ANN ARBOR, Mich., March 25, 2014 /PRNewswire-USNewswire/ --What makes a person bipolar, prone to manic highs and deep, depressed lows? Why does bipolar disorder run so strongly in families, even though no single gene is to blame? And why is it so hard to find new treatments for a condition that affects 200 million people worldwide?

New stem cell research published by scientists from the University of Michigan Medical School, and fueled by the Heinz C. Prechter Bipolar Research Fund, may help scientists find answers to these questions.

The team used skin from people with bipolar disorder to derive the first-ever stem cell lines specific to the condition. In a new paper in Translational Psychiatry, they report how they transformed the stem cells into neurons, similar to those found in the brain – and compared them to cells derived from people without bipolar disorder.

The comparison revealed very specific differences in how these neurons behave and communicate with each other, and identified striking differences in how the neurons respond to lithium, the most common treatment for bipolar disorder.

It's the first time scientists have directly measured differences in brain cell formation and function between people with bipolar disorder and those without.

The researchers are from the Medical School's Department of Cell & Developmental Biology and Department of Psychiatry, and U-M's Depression Center.

Stem cells as a window on bipolar disorder

The team used a type of stem cell called induced pluripotent stem cells, or iPSCs. By taking small samples of skin cells and exposing them to carefully controlled conditions, the team coaxed them to turn into stem cells that held the potential to become any type of cell. With further coaxing, the cells became neurons.

"This gives us a model that we can use to examine how cells behave as they develop into neurons. Already, we see that cells from people with bipolar disorder are different in how often they express certain genes, how they differentiate into neurons, how they communicate, and how they respond to lithium," says Sue O'Shea, Ph.D., the experienced U-M stem cell specialist who co-led the work.

"We're very excited about these findings. But we're only just beginning to understand what we can do with these cells to help answer the many unanswered questions in bipolar disorder's origins and treatment," says Melvin McInnis, M.D., principal investigator of the Prechter Bipolar Research Fund and its programs.

"For instance, we can now envision being able to test new drug candidates in these cells, to screen possible medications proactively instead of having to discover them fortuitously."

The research was supported by donations from the Heinz C. Prechter Bipolar Research Fund, the Steven M. Schwartzberg Memorial Fund, and the Joshua Judson Stern Foundation. The A. Alfred Taubman Medical Research Institute at the U-M Medical School also supported the work, which was reviewed and approved by the U-M Human Pluripotent Stem Cell Research Oversight committee and Institutional Review Board.

O'Shea, a professor in the Department of Cell & Developmental Biology and director of the U-M Pluripotent Stem Cell Research Lab, and McInnis, the Upjohn Woodworth Professor of Bipolar Disorder and Depression in the Department of Psychiatry, are co-senior authors of the new paper.

McInnis, who sees firsthand the impact that bipolar disorder has on patients and the frustration they and their families feel about the lack of treatment options, says the new research could take treatment of bipolar disorder into the era of personalized medicine.

Not only could stem cell research help find new treatments, it may also lead to a way to target treatment to each patient based on their specific profile – and avoid the trial-and-error approach to treatment that leaves many patients with uncontrolled symptoms. 

More about the findings:

The skin samples were used to derive the 42 iPSC lines. When the team measured gene expression first in the stem cells, and then re-evaluated the cells once they had become neurons, very specific differences emerged between the cells derived from bipolar disorder patients and those without the condition.

Specifically, the bipolar neurons expressed more genes for membrane receptors and ion channels than non-bipolar cells, particularly those receptors and channels involved in the sending and receiving of calcium signals between cells.

Calcium signals are already known to be crucial to neuron development and function. So, the new findings support the idea that genetic differences expressed early during brain development may have a lot to do with the development of bipolar disorder symptoms – and other mental health conditions that arise later in life, especially in the teen and young adult years.

Meanwhile, the cells' signaling patterns changed in different ways when the researchers introduced lithium, which many bipolar patients take to regulate their moods, but which causes side effects. In general, lithium alters the way calcium signals are sent and received – and the new cell lines will make it possible to study this effect specifically in bipolar disorder-specific cells.

Like misdirected letters and packages at the post office, the neurons made from bipolar disorder patients also differed in how they were 'addressed' during development for delivery to certain areas of the brain. This may have an impact on brain development, too.

The researchers also found differences in microRNA expression in bipolar cells – tiny fragments of RNA that play key roles in the "reading" of genes. This supports the emerging concept that bipolar disorder arises from a combination of genetic vulnerabilities. 

The researchers are already developing stem cell lines from other trial participants with bipolar disorder, though it takes months to derive each line and obtain mature neurons that can be studied. They will share their cell lines with other researchers via the Prechter Repository at U-M. They also hope to develop a way to use the cells to screen drugs rapidly, called an assay.

Haiming Chen, M.D., and Cindy DeLong, Ph.D., manager of the pluripotent stem cell core laboratory, are co-first authors of the paper. Reference: Translational Psychiatry, early online publication, March 25, 2014.

SOURCE University of Michigan Health System

More Stories By PR Newswire

Copyright © 2007 PR Newswire. All rights reserved. Republication or redistribution of PRNewswire content is expressly prohibited without the prior written consent of PRNewswire. PRNewswire shall not be liable for any errors or delays in the content, or for any actions taken in reliance thereon.

Latest Stories
The emerging Internet of Everything creates tremendous new opportunities for customer engagement and business model innovation. However, enterprises must overcome a number of critical challenges to bring these new solutions to market. In his session at @ThingsExpo, Michael Martin, CTO/CIO at nfrastructure, outlined these key challenges and recommended approaches for overcoming them to achieve speed and agility in the design, development and implementation of Internet of Everything solutions with...
When it comes to cloud computing, the ability to turn massive amounts of compute cores on and off on demand sounds attractive to IT staff, who need to manage peaks and valleys in user activity. With cloud bursting, the majority of the data can stay on premises while tapping into compute from public cloud providers, reducing risk and minimizing need to move large files. In his session at 18th Cloud Expo, Scott Jeschonek, Director of Product Management at Avere Systems, discussed the IT and busine...
DevOps is often described as a combination of technology and culture. Without both, DevOps isn't complete. However, applying the culture to outdated technology is a recipe for disaster; as response times grow and connections between teams are delayed by technology, the culture will die. A Nutanix Enterprise Cloud has many benefits that provide the needed base for a true DevOps paradigm. In his general session at 20th Cloud Expo, Chris Brown, a Solutions Marketing Manager at Nutanix, will explore...
It is one thing to build single industrial IoT applications, but what will it take to build the Smart Cities and truly society changing applications of the future? The technology won’t be the problem, it will be the number of parties that need to work together and be aligned in their motivation to succeed. In his Day 2 Keynote at @ThingsExpo, Henrik Kenani Dahlgren, Portfolio Marketing Manager at Ericsson, discussed how to plan to cooperate, partner, and form lasting all-star teams to change the...
Unsecured IoT devices were used to launch crippling DDOS attacks in October 2016, targeting services such as Twitter, Spotify, and GitHub. Subsequent testimony to Congress about potential attacks on office buildings, schools, and hospitals raised the possibility for the IoT to harm and even kill people. What should be done? Does the government need to intervene? This panel at @ThingExpo New York brings together leading IoT and security experts to discuss this very serious topic.
All clouds are not equal. To succeed in a DevOps context, organizations should plan to develop/deploy apps across a choice of on-premise and public clouds simultaneously depending on the business needs. This is where the concept of the Lean Cloud comes in - resting on the idea that you often need to relocate your app modules over their life cycles for both innovation and operational efficiency in the cloud. In his session at @DevOpsSummit at19th Cloud Expo, Valentin (Val) Bercovici, CTO of Soli...
“We're a global managed hosting provider. Our core customer set is a U.S.-based customer that is looking to go global,” explained Adam Rogers, Managing Director at ANEXIA, in this SYS-CON.tv interview at 18th Cloud Expo, held June 7-9, 2016, at the Javits Center in New York City, NY.
@DevOpsSummit has been named the ‘Top DevOps Influencer' by iTrend. iTrend processes millions of conversations, tweets, interactions, news articles, press releases, blog posts - and extract meaning form them and analyzes mobile and desktop software platforms used to communicate, various metadata (such as geo location), and automation tools. In overall placement, @DevOpsSummit ranked as the number one ‘DevOps Influencer' followed by @CloudExpo at third, and @MicroservicesE at 24th.
In his session at 20th Cloud Expo, Chris Carter, CEO of Approyo, will discuss the basic set up and solution for an SAP solution in the cloud and what it means to the viability of your company. Chris Carter is CEO of Approyo. He works with business around the globe, to assist them in their journey to the usage of Big Data in the forms of Hadoop (Cloudera and Hortonwork's) and SAP HANA. At Approyo, we support firms who are looking for knowledge to grow through current business process, where even ...
DevOps is often described as a combination of technology and culture. Without both, DevOps isn't complete. However, applying the culture to outdated technology is a recipe for disaster; as response times grow and connections between teams are delayed by technology, the culture will die. A Nutanix Enterprise Cloud has many benefits that provide the needed base for a true DevOps paradigm.
Personalization has long been the holy grail of marketing. Simply stated, communicate the most relevant offer to the right person and you will increase sales. To achieve this, you must understand the individual. Consequently, digital marketers developed many ways to gather and leverage customer information to deliver targeted experiences. In his session at @ThingsExpo, Lou Casal, Founder and Principal Consultant at Practicala, discussed how the Internet of Things (IoT) has accelerated our abilit...
SYS-CON Events announced today that Enzu will exhibit at SYS-CON's 20th International Cloud Expo®, which will take place on June 6-8, 2017, at the Javits Center in New York City, NY, and the 21st International Cloud Expo®, which will take place October 31-November 2, 2017, at the Santa Clara Convention Center in Santa Clara, CA. Enzu’s mission is to be the leading provider of enterprise cloud solutions worldwide. Enzu enables online businesses to use its IT infrastructure to their competitive ad...
"I think that everyone recognizes that for IoT to really realize its full potential and value that it is about creating ecosystems and marketplaces and that no single vendor is able to support what is required," explained Esmeralda Swartz, VP, Marketing Enterprise and Cloud at Ericsson, in this SYS-CON.tv interview at @ThingsExpo, held June 7-9, 2016, at the Javits Center in New York City, NY.
Data is the fuel that drives the machine learning algorithmic engines and ultimately provides the business value. In his session at Cloud Expo, Ed Featherston, a director and senior enterprise architect at Collaborative Consulting, discussed the key considerations around quality, volume, timeliness, and pedigree that must be dealt with in order to properly fuel that engine.
SYS-CON Events announced today that CA Technologies has been named “Platinum Sponsor” of SYS-CON's 20th International Cloud Expo®, which will take place on June 6-8, 2017, at the Javits Center in New York City, NY, and the 21st International Cloud Expo®, which will take place October 31-November 2, 2017, at the Santa Clara Convention Center in Santa Clara, CA. CA Technologies helps customers succeed in a future where every business – from apparel to energy – is being rewritten by software. From ...