Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:


Team Creates Stem Cells from Schizophrenia Patients

Scientists use new technique to reprogram cells with risk gene for major mental illness

Using skin cells from adult siblings with schizophrenia and a genetic mutation linked to major mental illnesses, Johns Hopkins researchers have created induced pluripotent stem cells (iPS cells) using a new and improved “clean” technique.

Reporting online February 22 in Molecular Psychiatry, the team confirms the establishment of two new lines of iPS cells with mutations in the gene named Disrupted In Schizophrenia 1, or DISC1. They made the cells using a nonviral “epiosomal vector” that jumpstarts the reprogramming machinery of cells without modifying their original genetic content with foreign DNA from a virus.

The stem cells from these two new lines, the scientists say, can be coaxed to become brain cells such as neurons. Because they have the DISC1 mutation, they stand to play an important role in the screening of drugs for treatments of major mental illnesses such as schizophrenia, bipolar disorder and major depression, as well as provide clues about the causes of these diseases.

“Most people think of stem cells only as potential transplant therapy to replace damaged cells or tissue, but for psychiatric diseases, which have proven a challenge to scientific understanding just as a sheer cliff challenges a climber, these cells provide a toehold,” says Russell L. Margolis, M.D., professor of psychiatry and neurology, and director of the Johns Hopkins Schizophrenia Program. “Nature put in only a few little grab holds, and now we are generating our own so we can scale the cliff of mental illness faster.”

The benefit of maintaining the original genome of cells being reprogrammed outweighs the fact that the episomal vector approach is both time- and labor-intensive, says Guo-li Ming, Ph.D., associate professor of neurology, Institute for Cell Engineering, Johns Hopkins University School of Medicine.

“The efficiency of the new technique is very, very low,” Ming reports, citing a rate of 0.0006 percent or less and comparing it to the rate of efficiency of virally infected reprogrammed cells, which hovers at about 0.001 percent. “Human cells grow slowly, and this kind of reprogramming takes time.”

However, the episomal vector method solves tricky problems associated with the more efficient viral approach, which involves inserting foreign genes into the cell’s genome and potentially interrupting or influencing other genes that can change cell behavior. It also relieves worry about weird cell behavior later due to reactivation of introduced genes that remain in the genome, the researchers say.

The skin biopsy samples used in the study came from an American family first reported 25 years ago to have multiple family members affected with schizophrenia. A genetic analysis conducted by Margolis and colleagues six years ago discovered that a mutation in the DISC1 gene was common to all members of the family with severe mental illness. Two years ago, Margolis and Christopher A. Ross, M.D., Ph.D., director of the division of neurobiology, collected the skin samples and delivered them to Ming’s team, which thus far has successfully reprogrammed two of those samples into the new iPS cell lines. Skin cell samples from the remaining family members, as well as from unrelated individuals with schizophrenia, are still works in progress in the Ming lab, potentially becoming additional stem cell lines, according to Ming.

First, using the cultured skin cells, the team delivered a package of so-called reprogramming factors into the cytoplasm — as opposed to the nucleus, where the cell’s genetic material resides — via bits of DNA (episomal vectors) that are serially diluted during cell division after making their special delivery. These cells then were grown in culture while the scientists monitored them for changes.

It took a wildly variable window of time — anywhere between three weeks and three months — for the elongated and single-layered skin cells to begin to change shape and cluster together, a telling sign that they were on the path to becoming stem cells, Ming explains.

“Seeing the colonies was heartening evidence of reprogramming, but not proof of ground state of pluripotent stem cells,” Ming says. “We had to go through a series of characterization process, which generally takes about six months or more, depending on your rigor, to prove that.

The team then conducted a series of tests to verify not only that the genes they used to introduce the reprogramming factors were undetectable from the transformed cells, but also to prove their pluripotency. First, they confirmed that these cells could generate differentiated cells from all three germ layers — the endoderm, mesoderm and ectoderm — which eventually give rise to all of an animal’s tissues and organs. By changing the recipe of the culture media in which the cells were growing, the team coaxed the cells to become not only neurons, but also fat cells and bone and muscle tissue, for instance. To confirm these were bona fide iPS cells with the ability to differentiate into all different cells types, the researchers performed a stringent test that involved injecting the presumed stem cells into mice whose immune systems were suppressed and noted that cells from three germ layers were present in the tumors that formed.

“The hard work of generating and characterizing these iPS cells is a prelude for future studies,” Ming says. “Now, we can look at neural cells differentiated from these iPS cells in order to investigate the mechanisms and functions of the DISC1 gene in the nervous system, and understand the role it may play in diseases such as schizophrenia. These future studies may lead to the identification of new molecules that might serve as drug targets.”

This research was supported by the National Institutes of Health, the Maryland Stem Cell Research Fund, the National Alliance for Research on Schizophrenia and Depression, and the International Mental Health Research Organization.

Johns Hopkins authors on the paper, in addition to Ming and Margolis, are Cheng-Hsuan Chiang, Yijing Su, Zhexing Wen, Nadine Yoritomo, Christopher A. Ross and Hongjun Song, all of Johns Hopkins.

On the Web:

Molecular Psychiatry:

Maryalice Yakutchik | Newswise Science News
Further information:

More articles from Life Sciences:

nachricht Biologists unravel another mystery of what makes DNA go 'loopy'
16.03.2018 | Emory Health Sciences

nachricht Scientists map the portal to the cell's nucleus
16.03.2018 | Rockefeller University

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Locomotion control with photopigments

Researchers from Göttingen University discover additional function of opsins

Animal photoreceptors capture light with photopigments. Researchers from the University of Göttingen have now discovered that these photopigments fulfill an...

Im Focus: Surveying the Arctic: Tracking down carbon particles

Researchers embark on aerial campaign over Northeast Greenland

On 15 March, the AWI research aeroplane Polar 5 will depart for Greenland. Concentrating on the furthest northeast region of the island, an international team...

Im Focus: Unique Insights into the Antarctic Ice Shelf System

Data collected on ocean-ice interactions in the little-researched regions of the far south

The world’s second-largest ice shelf was the destination for a Polarstern expedition that ended in Punta Arenas, Chile on 14th March 2018. Oceanographers from...

Im Focus: ILA 2018: Laser alternative to hexavalent chromium coating

At the 2018 ILA Berlin Air Show from April 25–29, the Fraunhofer Institute for Laser Technology ILT is showcasing extreme high-speed Laser Material Deposition (EHLA): A video documents how for metal components that are highly loaded, EHLA has already proved itself as an alternative to hard chrome plating, which is now allowed only under special conditions.

When the EU restricted the use of hexavalent chromium compounds to special applications requiring authorization, the move prompted a rethink in the surface...

Im Focus: Radar for navigation support from autonomous flying drones

At the ILA Berlin, hall 4, booth 202, Fraunhofer FHR will present two radar sensors for navigation support of drones. The sensors are valuable components in the implementation of autonomous flying drones: they function as obstacle detectors to prevent collisions. Radar sensors also operate reliably in restricted visibility, e.g. in foggy or dusty conditions. Due to their ability to measure distances with high precision, the radar sensors can also be used as altimeters when other sources of information such as barometers or GPS are not available or cannot operate optimally.

Drones play an increasingly important role in the area of logistics and services. Well-known logistic companies place great hope in these compact, aerial...

All Focus news of the innovation-report >>>



Industry & Economy
Event News

Ultrafast Wireless and Chip Design at the DATE Conference in Dresden

16.03.2018 | Event News

International Tinnitus Conference of the Tinnitus Research Initiative in Regensburg

13.03.2018 | Event News

International Virtual Reality Conference “IEEE VR 2018” comes to Reutlingen, Germany

08.03.2018 | Event News

Latest News

Wandering greenhouse gas

16.03.2018 | Earth Sciences

'Frequency combs' ID chemicals within the mid-infrared spectral region

16.03.2018 | Physics and Astronomy

Biologists unravel another mystery of what makes DNA go 'loopy'

16.03.2018 | Life Sciences

Science & Research
Overview of more VideoLinks >>>