Scientific research isn’t always easy to explain—or to understand. Whichever side of the conversation you’re on, you might feel a communication gap. The California Institute for Regenerative Medicine (CIRM) , the state’s stem cell agency, recently set out to bridge that gap with a #SciencePitch Challenge. Their goal was to encourage stem cell researchers to develop their “elevator pitch” — the short overview of their work that they’d give if a fellow elevator passenger asked them what they do and they only had a short ride in which to explain it. In the process, the participants are also demonstrating the importance of stem cell research and generating excitement about their work.
Stuart A. Lipton, M.D., Ph.D., director of Sanford-Burnham’s Del E. Webb Center for Neuroscience, Aging, and Stem Cell Research and a clinical neurologist
Neurons made from stem cells drive brain activity after transplantation in laboratory model
Originally published November 15, 2012
Researchers and patients look forward to the day when stem cells might be used to replace dying brain cells in Alzheimer’s disease and other neurodegenerative conditions. Scientists are currently able to make neurons and other brain cells from stem cells, but getting these neurons to properly function when transplanted to the host has proven to be more difficult. Now, researchers at Sanford-Burnham Medical Research Institute have found a way to stimulate stem cell-derived neurons to direct cognitive function after transplantation to an existing neural network. The study was published November 7 in the Journal of Neuroscience.
Stuart A. Lipton, M.D., Ph.D., director of Sanford-Burnham’s Del E. Webb Center for Neuroscience, Aging, and Stem Cell Research and a clinical neurologist
Sanford-Burnham researchers convince transplanted stem cell-derived neurons to direct cognitive function—getting us a step closer to using these cells to treat Alzheimer’s disease and other neurodegenerative conditions.
Researchers and patients look forward to the day when stem cells might be used to replace dying brain cells in Alzheimer’s disease and other neurodegenerative conditions. Scientists are currently able to make neurons and other brain cells from stem cells, but getting these neurons to properly function when transplanted to the host has proven to be more difficult. Now, researchers at Sanford-Burnham Medical Research Institute have found a way to stimulate stem cell-derived neurons to direct cognitive function after transplantation to an existing neural network. The study was published November 7 in the Journal of Neuroscience.
Left: Medulloblastoma tumor (green) from untreated mouse. Right: Corresponding tissue from mouse treated with bFGF lacks tumor growth.
Brain tumors arising from different cell types might require different—and more personalized—treatment approaches.
Cancers arise when a normal cell acquires a mutation in a gene that regulates cellular growth or survival. But the particular cell this mutation happens in—the cell of origin—can have an enormous impact on the behavior of the tumor, and on the strategies used to treat it.
Robert Wechsler-Reya, Ph.D., professor and director of the Tumor Development Program in Sanford-Burnham’s NCI-designated Cancer Center, and his team study medulloblastoma, the most common malignant brain cancer in children. A few years ago, they made an important discovery: medulloblastoma can originate from one of two cell types: 1) stem cells, which can make all the different cell types in the brain or 2) neuronal progenitor cells, which can only make neurons.
Stem cells and progenitor cells are regulated by different growth factors. So, Wechsler-Reya thought, maybe the tumors arising from these cells respond differently to different therapies…
Conventional therapies don't hit tumors in the right place - at the cancer stem cells - so they keep coming back
The scientific symposium portion of San Diego’s annual Stem Cell Meeting on the Mesa fell on Halloween this year—good timing for a discussion about the dark side of stem cells: cancer stem cells.
Robert Wechsler-Reya, Ph.D., director of Sanford-Burnham’s Tumor Development Program, once said, “Current cancer therapies are like trying to kill a zombie by kicking it in the shins.”
Everyone knows you can only kill a zombie with a shot to the brains—anywhere else might slow it down temporarily, but only a very targeted hit to the head will get rid of it for good. (See the CDC’s Zombie Preparedness Guide.) So what Wechsler-Reya means is that the current methods for destroying or removing tumor cells are not aimed at what may, in some cases, be the actual “brains” of the problem—cancer stem cells.
Like other types of stem cells, cancer stem cells can self-renew, producing more cells. They also differentiate, specializing into other cell types. Those are very useful features when scientists are using stem cells to repair or replace diseased or damaged tissue (rebuilding heart muscle tissue after a heart attack, for example). However, cellular proliferation is also a hallmark of cancer.
In some cancers, stem cells may be the initial source of the problem, giving rise to tumors. They might also be the reason some tumors are resistant to standard cancer therapies such as chemotherapy or radiation therapy. What’s more, cancer stem cells can allow tumors to recur—even if the bulk of a tumor is removed, a few remaining cancer stem cells rise up to rebuild a new tumor. Like zombies, they are hard to get rid of.
Scientists are now trying to learn how stem cells turn to the dark side in cancer so that they can figure out how to better detect, prevent, and treat tumor growth—targeting the zombie’s brains, not just its shins.
Meet the four cancer stem cell (zombie)-fighting scientists who spoke at the 2012 Stem Cell Meeting on the Mesa:
Huei-Sheng Vincent Chen, Ph.D.
The California Institute for Regenerative Medicine (CIRM) has awarded a $1.58 million grant to Huei-Sheng Vincent Chen, Ph.D., associate professor at Sanford-Burnham. Chen’s proposal was one of 28 new projects funded as part of CIRM’s Basic Biology IV awards program, which supports basic research aimed at increasing our understanding of stem cells and how to work with them. This new funding will allow Chen and his team to develop personalized models of inherited heart conditions using stem cells derived from patients’ own skin cells. They will also use these models to develop new therapies.
“Most heart conditions that cause sudden death in young people—those under age 35—are caused by inherited genetic mutations. But doctors have a hard time treating these types of heart conditions because not much is known about how genetic mutations cause them and because they’re usually diagnosed late in the disease process,” Chen said. “At the moment, the only way to treat these inherited heart diseases is to implant a heart-shocking device to prevent sudden death. More frequently, however, no therapy is available to slow the disease’s progression.”
Cerebellar stem cells engineered to express Myc and mutant p53 (shown here) give rise to aggressive tumors that resemble a particularly malignant form of human medulloblastoma, providing a new model that will help scientists develop more effective therapies for this disease.
Children with a devastating brain cancer called medulloblastoma develop tumors in a region of the brain called the cerebellum, which plays an important role in motor control. Seventy-five percent of children with the disease survive after aggressive surgery, radiation, and chemotherapy—but side effects can be severe, leading to cognitive deficits, endocrine disorders, and the development of other cancers later in life.
Sanford-Burnham scientists have now developed a new mouse model for studying medulloblastoma. The animal model mimics the deadliest of four subtypes of the human disease, a tumor that is triggered by elevated levels of a gene known as Myc. The study, published February 13 in the journal Cancer Cell, also suggests a potential strategy for inhibiting the growth of this tumor type. This achievement marks an important milestone toward personalized therapies tailored to a specific type of medulloblastoma.
“Being able to use an animal model as a tool to test treatments has been very valuable in medulloblastoma, as in other types of tumors. But for Myc-associated tumors, that hasn’t been an option because there hasn’t been a model of the disease. This is the first step to developing therapies for this type of tumor,” said Robert Wechsler-Reya, Ph.D., director of the Tumor Development Program in Sanford-Burnham’s National Cancer Institute-designated Cancer Center, member of the Sanford Consortium for Regenerative Medicine, and senior author of the study.
Brandon Nelson, manager of Sanford-Burnham's Stem Cell Research Center, welcomes visitors.
On October 5, we opened our La Jolla campus to the San Diego community in honor of Stem Cell Awareness Day. Despite the rain and wind, a number of people from the San Diego Blood Bank, Juvenile Diabetes Research Foundation, the California Institute for Regenerative Medicine, local schools, and elsewhere dropped by to learn about stem cell research and the promise these special cells hold for discovering the root causes of disease, finding new treatments, and ultimately improving the human condition.
Left: Brandon Nelson, manager of Sanford-Burnham's Stem Cell Research Center, pulls stem cells out of cryogenic storage (Photo by Nadia Borowski Scott) Right: Cluster of neurons (pink) derived from stem cells.
Wednesday, October 5, 2011 is Stem Cell Awareness Day, sponsored by the California Institute for Regenerative Medicine. To mark the occasion at Sanford-Burnham, we are opening our doors to anyone who wants to learn about the latest in stem cell research and the therapeutic potential stem cells hold for Alzheimer’s disease, heart disease, joint diseases, spinal cord injury, diabetes, and more.
- What: Stem Cell Awareness Day
Public tours of Sanford-Burnham’s stem cell research facility and drug discovery center - When: Wednesday, October 5, 2011, 3:00-4:00 p.m.
- Where: Sanford-Burnham’s La Jolla, California campus
10901 North Torrey Pines Road
La Jolla, California 92037
See map here and follow event signs to parking. Tours will begin outside Building 7. - Who: students, teachers, patients, advocates, press, and other members of the community are invited
- RSVP: If you plan to attend or have any questions, please contact Heather Buschman at
hbuschman@sanfordburnham.org or 858-610-3808.
Attendees will tour our Stem Cell Research Center and meet scientists who are turning stem cells into other cell types that can be used to replace diseased or damaged tissue in heart disease, Alzheimer’s disease, and more. Visitors will have the chance to look through a microscope at cardiomyocytes (heart muscle cells) that are able to beat even in a laboratory dish. We will also take visitors to the Conrad Prebys Center for Chemical Genomics, where stem cells and robots are being used to discover new medicines by modeling diseases in a dish.
Check out more Stem Cell Awareness Day events taking place throughout California, the U.S., and the world or read more about Sanford-Burnham stem cell research on our blog.
Dr. Evan Y. Snyder (right), with collaborator Dr. Seung U. Kim
Stem cells have the unique ability to self-renew (make more stem cells) and differentiate (specialize into a number of different cell types). There are three main types of stem cells already on the scene: embryonic stem cells, adult stem cells and induced pluripotent stem (iPS) cells. iPS cells are engineered by reprogramming fully differentiated adult cells, often skin cells, back to a primitive state. Like their embryonic cousins, iPS cells can form all cell types. Researchers are currently working to harness the flexibility of stem cells to replace damaged tissue and treat conditions like diabetes and heart disease.
The iPS cell approach to regenerative medicine is tantalizing because these cells could be derived from a patient’s own cells and are therefore less likely to face immune rejection. In the past few weeks, however, a slew of papers have indicated that the therapeutic potential of iPS cells might be limited by reprogramming errors and genomic instability. Given these problems, researchers from Sanford-Burnham, Chung-Ang University in Korea, University of British Columbia, Harvard Medical School and elsewhere wondered if there might be a better way to regenerate lost tissue to treat conditions like heart disease and stroke. Writing March 4 in the Proceedings of the National Academy of Sciences, they outline a method to obtain a new kind of stem cell they call induced conditional self-renewing progenitor (ICSP) cells.
How can patient advocates help drive basic research?
Last week I attended the Stem Cell Meeting on the Mesa, an annual event organized by CONNECT. The meeting included all the stellar scientific panels I expected and one I didn’t expect: “Patient Advocacy 2.0 – Can they participate?”
The panel discussed opportunities for patient participation and the ethics involved. I was captivated by panel member Dani Grady’s story of surviving breast cancer and her advocacy for increased cancer research funding, education, improved patient care and more patient participation in clinical trials. It was interesting to hear how a patient’s perspective can improve clinical trials and the drug approval process. But as I sat there, I couldn’t help wondering… how can patients participate in basic research – the earliest phase of biomedical discovery, during which the molecular underpinnings of disease are only just beginning to be understood?
So I did a little research of my own.
As a young scientist in the 1990s, Dr. Evan Snyder, now director of Sanford-Burnham’s Stem Cells and Regenerative Biology Program, had never worked on cancer. But when his close friend Dr. James Galambos died from a glioblastoma, he promised the family he would do everything he could to find a cure. In 2000, Dr. Snyder, Dr. Karen Aboody, now at City of Hope, and colleagues published a paper that described how stem cells could be used to treat cancer. A recent article on the California Institute for Regenerative Medicine(CIRM) website highlighted this breakthrough:
Neural stem cells, it revealed, are attracted to tumors like moths to a light. If they could be made to carry a chemotherapeutic payload, they could serve as weapons against the wanton spread of metastatic brain cancer.
CIRM committed $37 million to successfully move this promising research into clinical trials. To learn more about how stem cells can be used to target tumors, read Manipulated Medicine.
The City of Hope trial has also been featured on CBS News.
On May 14, UC Irvine opened the first of seven California Institute for Regenerative Medicine (CIRM) institutes. The 85,000-square-foot Sue and Bill Gross Stem Cell Research Center will feature a basic research program to explore new methods to isolate stem cellsand understand their fundamental properties; a drug discovery program to identify and develop stem cell-based therapies; and a regenerative medicine application program to study the efficacy and safety of new therapies and bring them to the clinic. The research will focus on Alzheimer’s disease, spinal cord injuries and macular degeneration.San Diego has our own CIRM Institute on the horizon. On March 26, the Sanford Consortium for Regenerative Medicine held the official groundbreaking ceremony for its new 135,000-square-foot research building on Torrey Pines Mesa. The Consortium, a collaboration between Sanford-Burnham, the Salk Institute, The Scripps Research Institute and the University of California, San Diego, was created to combine the talent and technology of these four great research institutions to advance our understanding of stem cell biology and ultimately find new treatments for Alzheimer’s disease, Parkinson’s disease, diabetes, paralysis and many other conditions. The building is being funded largely through a $30 million gift from T. Denny Sanford and a $43 million grant from CIRM. The facility is expect to open in June 2011.
The California Institute for Regenerative Medicine (CIRM) recently put out its annual report, which provides an excellent overview of stem cell research in California. Sanford-Burnham supplied the cover image (above), which was originally taken by the Terskikh laboratory. Best cover ever.CIRM was created in 2005, following the passage of Proposition 71, to make grants and provide loans for stem cell research, research facilities and other vital research opportunities. CIRM support has been invaluable to stem cell researchers seeking cures for cancer, diabetes, heart disease, neurodegenerative diseases, paralysis and many other conditions.