Broad Center for Regenerative Medicine and Stem Cell Research

Building a better brain (model) in the lab

/ Kevin McCormack / Leave a comment
Leica Picture of a brain organoid: courtesy National Institute of Allergy and Infectious Diseases, NIH

One of the biggest problems with trying to understand what is happening in a disease that affects the brain is that it’s really difficult to see what is going on inside someone’s head. People tend to object to you trying to open their noggin while they are still using it.

New technologies can help, devices such as MRI’s – which chart activity and function by measuring blood flow – or brain scans using electroencephalograms (EEGs), which measure activity by tracking electrical signaling and brain waves. But these are still limited in what they can tell us.

Enter brain organoids. These are three dimensional models made from clusters of human stem cells grown in the lab. They aren’t “brains in a dish” – they can’t function or think independently – but they can help us develop a deeper understanding of how the brain works and even why it doesn’t always work as well as we’d like.

Now researchers at UCLA’s Broad Center of Regenerative Medicine have created brain organoids that demonstrate brain wave activity similar to that found in humans, and even brain waves found in particular neurological disease.

The team – with CIRM funding – took skin tissue from healthy individuals and, using the iPSC method – which enables you to turn these cells into any other kind of cell in the body – they created brain organoids. They then studied both the physical structure of the organoids by examining them under a microscope, and how they were functioning by using a probe to measure brain wave activity.

In a news release Dr. Ranmal Samarasinghe, the first author of the study in the journal Nature Neuroscience, says they wanted to do this double test for a very good reason: “With many neurological diseases, you can have terrible symptoms but the brain physically looks fine. So, to be able to seek answers to questions about these diseases, it’s very important that with organoids we can model not just the structure of the brain but the function as well.”

Next, they took skin cells from people with a condition called Rhett syndrome. This is a rare genetic disorder that affects mostly girls and strikes in the first 18 months of life, having a severe impact on the individual’s ability to speak, walk, eat or even breathe easily. When the researchers created brain organoids with these cells the structure of the organoids looked similar to the non-Rhett syndrome ones, but the brain wave activity was very different. The Rhett syndrome organoids showed very erratic, disorganized brain waves.

When the team tested an experimental medication called Pifithrin-alpha on the Rhett organoids, the brain waves became less erratic and more like the brain waves from the normal organoids.

“This is one of the first tangible examples of drug testing in action in a brain organoid,” said Samarasinghe. “We hope it serves as a stepping stone toward a better understanding of human brain biology and brain disease.”

Remembering Eli Broad, philanthropist and stem cell champion

/ Kevin McCormack / Leave a comment
Eli Broad, Photo by Nancy Pastor

The world of stem cell research lost a good friend this weekend. Eli Broad, a generous supporter of science, education and the arts, passed away at the age of 87.

Eli came from humble origins, born in the Bronx to an immigrant father who worked as a house painter and a mother who was a seamstress. He went to Michigan State University, working a number of jobs to pay his way, including selling women’s shoes, working as a door-to-door salesman for garbage disposal units, and delivering rolls of film to be developed. He graduated in three years and then became the youngest person ever to pass the CPA exam in Michigan.

He started out as an accountant but quickly switched to housing and development and was a millionaire by the time he was 30. As his wealth grew so did his interest in using that money to support causes dear to him and his wife Edythe.

With the passage of Proposition 71 in 2004 Broad put up money to help create the Broad Stem Cell Centers at UCLA, UC San Francisco and the University of Southern California. Those three institutions became powerhouses in stem cell research and the work they do is a lasting legacy to the generosity of the Broads.

Rosa Dilani, histology core manager at the Eli and Edythe Broad CIRM Center, explains the lab’s function to Eli Broad after the Oct. 29 ribbon cutting of the new building. In the background are U.S. Rep. Lucille Roybal-Allard (in purple) and Bob Klein in gray suit.

“Science has lost one of its greatest philanthropic supporters,” says Jonathan Thomas, PhD, JD, Chair of the CIRM Board. ” Eli and Edye Broad set the table for decades of transformative work in stem cell and gene therapy through their enthusiastic support for Proposition 71 and funding at a critical time in the early days of regenerative medicine. Their recent additional generous contributions to USC, UCLA and UCSF helped to further advance that work.  Eli and Edye understood the critical role of science in making the world a better place.  Through these gifts and their enabling support of the Broad Institute with Harvard and MIT, they have left a lasting legacy in the advancement of medicine that cannot be overstated.”

Through the Broad Foundation he helped fund groundbreaking work not just in science but also education and the arts. Gerun Riley, President of the Broad Foundation says Eli was always interested in improving the lives of others.

“As a businessman Eli saw around corners, as a philanthropist he saw the problems in the world and tried to fix them, as a citizen he saw the possibility in our shared community, and as a husband, father, mentor and friend he saw the potential in each of us.”

Eli and Edythe Broad

Stem cells and prostate cancer are more similar than we thought

/ Karen Ring / 2 Comments

Prostate cancer is a scary word for men, no matter how macho or healthy they are. These days however, prostate cancer is no longer a death sentence for them. In fact, many men survive this disease if diagnosed early. However, for those unlucky ones who have more advanced stages of prostate cancer (where the tumor has metastasized and spread to other organs), the typical treatments used to fight the tumors don’t work effectively because advanced tumors become resistant to these therapies.

To help those afflicted with late stage prostate cancer, scientists are trying to understand the nature of prostate cancer cells and what makes them so “deadly”. By understanding the biology behind these tumor cells, they hope to develop better therapies to treat the late-stage forms of this disease.

UCLA scientists Bryan Smith and Owen Witte. (Image credit: UCLA Broad Stem Cell Research Center)

UCLA scientists Bryan Smith and Owen Witte. (Image credit: UCLA Broad Stem Cell Research Center)

But don’t worry, help is already on its way. Two groups from the University of California, Los Angeles and the University of California, Santa Cruz published a breakthrough discovery yesterday on the similarity between prostate cancer cells and prostate stem cells. The study was published in the journal PNAS and was led by senior author and director of the UCLA Broad Stem Cell Research Center, Dr. Owen Witte.

Using bioinformatics, Witte and his team compared the gene expression profiles of late-stage, metastatic prostate cancer cells sourced from tumor biopsies of living patients to healthy cell types in the male prostate. Epithelial cells are one of the main cell types in the prostate (they form the prostate glands) and they come in two forms: basal and luminal. When they compared the gene expression profiles of the prostate cancer cells to healthy prostate epithelial cells, they found that the cancer cells had a similar profile to normal prostate epithelial basal stem cells.

Image of a prostate cancer tumor. Green and red represent different stem cell traits and the yellow areas show where two stem cell traits are expressed together. (Image credit: UCLA Broad Stem Cell Research Center)

Image of a prostate cancer tumor. Green and red represent different stem cell traits and the yellow areas show where two stem cell traits are expressed together. (Image credit: UCLA Broad Stem Cell Research Center)

In fact, they discovered a 91-gene signature specific to the basal stem cells in the prostate. This profile included genes important for stem cell signaling and invasiveness. That meant that the metastatic prostate cancer cells also expressed “stem-like” genes.

First author Bryan Smith explained how their results support similar findings for other types of cancers. “Evidence from cancer research suggests that aggressive cancers have stem–cell-like traits. We now know this to be true for the most aggressive form of prostate cancer.”

So what does this study mean for prostate cancer patients? I’ll let Dr. Witte answer this one…

Treatments for early stage prostate cancer are often successful, but therapies that target the more aggressive and late-stage forms of the disease are urgently needed. I believe this research gives us important insight into the cellular nature of aggressive prostate cancer. Pinpointing the cellular traits of cancer — what makes those cells grow and spread — is crucial because then we can possibly target those traits to reverse or stop cancer’s progression. Our findings will inform our work as we strive to find treatments for aggressive prostate cancer.

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Beautiful by design: turning a stem cell research workplace into a work of art

/ cirmweb / 1 Comment
Broad Center for Regenerative Medicine & Stem Cell Research, USC

Sometimes what seems like an interesting project, a fun thing to try out, turns out to be a great idea, one that has the power to completely transform the way others see what you do and where you do it. That’s what is happening at the Broad Center for Regenerative Medicine and Stem Cell Research at the University of Southern California (USC).

A few weeks ago I told you how USC is using art to break down barriers, bringing together students studying art and design with stem cell researchers to collaborate on a project to come up with a new way of communicating about stem cells. The end results are far beyond what they had hoped for.

First, the art students toured the research facility, talked to the scientists and fell in love with the science. In a portfolio put together by the students they said they were “inspired by the imagery and research process.”

Then they got to work, coming up with ways of incorporating the imagery from stem cell research into the actual building itself. The students said they were inspired by the way the researchers worked together, and how the building itself seemed to promote that kind of collaboration because of its design. So, they set out to mirror that idea of collaboration by creating:

 “a designed environment that would enliven the space, enrich the researchers’ experience, convey a sense of the current research to visitors, and be visually energizing and engaging.”

They came up with a number of different proposals using different stem cell images and colors to brighten up the building and help give visual clues as to where you are in the facility. They wanted those colors and images to be part of the experience from the moment you walked in the lobby, to getting out of the elevator and walking down a corridor.

The end design will not just engage the eye but also the mind, using quotes from scientists, writers and patients to inspire people to think, to hope, and to reflect on the role that science plays in all our lives. One they have in mind comes from science fiction writer Ray Bradbury:

“The best scientist is open to experience and begins with romance – the idea that anything is possible.”

Although the semester is almost over the students have asked if they can stay on over the summer, to help see the final designs implemented.

At USC they’re showing that an open mind and a vivid imagination can turn a work place into a work of art. The science inspired that art. Now the hope is that the art will inspire the science.

kevin mccormack