How two California researchers are advancing world class science to develop real life solutions

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In our recently launched 5-year Strategic Plan, the California Institute for Regenerative Medicine (CIRM) profiled two researchers who have leveraged CIRM funding to translate basic biological discoveries into potential real-world solutions for devastating diseases.

Dr. Joseph Wu is director of the Stanford Cardiovascular Institute and the recipient of several CIRM awards. Eleven of them to be exact! Over the past 10 years, Dr. Wu’s lab has extensively studied the application of induced pluripotent stem cells (iPSCs) for cardiovascular disease modeling, drug discovery, and regenerative medicine. 

Dr. Wu’s extensive studies and findings have even led to a cancer vaccine technology that is now being developed by Khloris Biosciences, a biotechnology company spun out by his lab. 

Through CIRM funding, Dr. Wu has developed a process to produce cardiomyocytes (cardiac muscle cells) derived from human embryonic stem cells for clinical use and in partnership with the agency. Dr. Wu is also the principal investigator in the first-in-US clinical trial for treating ischemic heart disease. His other CIRM-funded work has also led to the development of cardiomyocytes derived from human induced pluripotent stem cells for potential use as a patch.

Over at UCLA, Dr. Lili Yang and her lab team have generated invariant Natural Killer T cells (iNKT), a special kind of immune system cell with unique features that can more effectively attack tumor cells. 

More recently, using stem cells from donor cord-blood and peripheral blood samples, Dr. Yang and her team of researchers were able to produce up to 300,000 doses of hematopoietic stem cell-engineered iNKT (HSC–iNKT) cells. The hope is that this new therapy could dramatically reduce the cost of producing immune cell products in the future. 

Additionally, Dr. Yang and her team have used iNKT cells to develop both autologous (using the patient’s own cells), and off-the-shelf anti-cancer therapeutics (using donor cells), designed to target blood cell cancers.

The success of her work has led to the creation of a start-up company called Appia Bio. In collaboration with Kite Pharma, Appia Bio is planning on developing and commercializing the promising technology. 

CIRM has been an avid supporter of Dr. Yang and Dr. Wu’s research because they pave the way for development of next-generation therapies. Through our new Strategic Plan, CIRM will continue to fund innovative research like theirs to accelerate world class science to deliver transformative regenerative medicine treatments in an equitable manner to a diverse California and the world.

Visit this page to learn more about CIRM’s new 5-year Strategic Plan and stay tuned as we share updates on our 5-year goals here on The Stem Cellar.

CIRM funded study identifies potential drug target for deadly heart condition

Joseph Wu is co-senior author of a study that demonstrates how patient-derived heart cells can help scientists better study the heart and screen potential therapies. Photo courtesy of Steve Fisch

Heart disease continues to be the number one cause of death in the United States. An estimated 375,000 people have a genetic form of heart disease known as familial dilated cardiomyopathy. This occurs when the heart muscle becomes weakened in one chamber in the heart, causing the open area of the chamber to become enlarged or dilated. As a result of this, the heart can no longer beat regularly, causing shortness of breath, chest pain and, in severe cases, sudden and deadly cardiac arrest.

A diagram of a normal heart compared to one with the dilated cardiomyopathy

A CIRM funded study by a team of researchers at Stanford University looked further into this form of genetic heart disease by taking a patient’s skin cells and converting them into stem cells known as induced pluripotent stem cells (iPSCs), which can become any type of cell in the body. These iPSCs were then converted into heart muscle cells that pulse just as they do in the body. These newly made heart muscle cells beat irregularly, similar to what is observed in the genetic heart condition.

Upon further analysis, the researchers linked a receptor called PGDF to cause various genes to be more highly activated in the mutated heart cells compared to normal ones. Two drugs, crenolanib and sunitinib, interfere with the PGDF receptor. After treating the abnormal heart cells, they began beating more regularly, and their gene-activation patterns more closely matched those of cells from healthy donors.

These two drugs are already FDA-approved for treating various cancers, but previous work shows that the drugs may damage the heart at high doses. The next step would be determining the right dose of the drug. The current study is part of a broader effort by the researchers to use these patient-derived cells-in-a-dish to screen for and discover new drugs.

Dr. Joseph Wu, co-senior author of this study, and his team have generated heart muscle cells from over 1,000 patients, including those of Dr. Wu, his son, and his daughter. In addition to using skin cells, the same technique to create heart cells from patients can also be done with 10 milliliters of blood — roughly two teaspoons.

In a news release, Dr. Wu is quoted as saying,

“With 10 milliliters of blood, we can make clinically usable amounts of your beating heart cells in a dish…Our postdocs have taken my blood and differentiated my pluripotent stem cells into my brain cells, heart cells and liver cells. I’m asking them to test some of the medications that I might need to take in the future.”

The full results of this study were published in Nature.