"Clinical trial in a dish" revolutionizes research
Human induced pluripotent stem cells (iPSCs) are key components of Dr. Wu’s work. Through a concept he calls "clinical trial in a dish," Dr. Wu and his team use iPSCs to gain a better understanding of cardiovascular diseases and accelerate the discovery of effective drugs to treat them.
Dr. Wu and his team at the Stanford Medicine-Joseph Wu Lab create iPSCs using donated skin or blood cells from thousands of patients. In the lab, Dr. Wu and his team reprogram the stem cells, essentially "resetting" them to their embryonic stage. This process enables the iPSCs to develop into many different cell types.
Dr. Wu’s team specializes in differentiating iPSCs into components that make up a human heart. These components include cardiomyocytes, cardiac fibroblasts, endothelial cells, smooth muscle cells, and pericytes. The cells have the unique advantage of being genetically matched to the patients.
Using patient-specific iPSCs, Dr. Wu and his colleagues study the genetic, molecular, and pathological mechanisms of heart and vascular diseases. Dr. Wu and his team test a variety of medications — including new drugs and those that have been FDA approved — on iPSCs in the lab. These tests allow Dr. Wu to determine which drugs are effective at treating certain diseases without the inherent risk of side effects involved with clinical trials in humans.
Integrating technologies to advance precision medicine
Clinical trial in a dish is paving the way for novel discoveries by altering the landscape of precision medicine. At the Stanford CVI, Dr. Wu and his team are merging stem cell technology, clinical genomics, and the powerful gene-editing tool CRISPR to prevent and cure diseases with unprecedented accuracy.
Dr. Wu combines these technologies to elucidate how certain genetic mutations cause cardiovascular diseases, including genetic cardiomyopathy, cardiac arrhythmias, and vascular diseases. By integrating these innovations, Dr. Wu and his team can:
- Identify the gene mutation responsible for the defect that causes these life-threatening disorders
- Determine the most effective medications to treat the disease
- Screen at-risk patients for the genetic mutation to prevent devastating outcomes, such as heart failure and sudden cardiac death
"I believe this is the holy grail of precision cardiovascular medicine," says Dr. Wu. "I hope that in the upcoming decades, work like this will be a common part of our toolboxes to discover new cardiovascular treatments."
The potential benefits of clinical trial in a dish and iPSCs extend far beyond cardiovascular medicine. In 2016, Dr. Wu studied patient-specific iPSCs to determine which breast cancer patients had a higher risk of cardiotoxicity after receiving doxorubicin for chemotherapy. By identifying patients who are more vulnerable to this well-known side effect of doxorubicin, physicians can closely monitor the heart health of their patients during treatment. Depending on the cardiotoxicity profile, physicians may choose a different treatment that is safer than doxorubicin.
Collaboration drives innovation
A distinguished researcher, Dr. Wu believes that collaboration is a catalyst for innovation. At the Stanford CVI, some of the world’s top scientists, engineers, physicians, and educators work together to unearth seminal discoveries and refine cardiovascular care.
"The more we help one another, the more we help ourselves, our current patients, and future generations," says Dr. Wu. "Only by uniting our efforts will we make the biggest advances in preventing and treating heart diseases."
Over the last decade, the CVI team has built a biobank of iPSC lines from more than two thousand patients. They have shared many of these cells, reagents, and protocols with hundreds of scientific colleagues at institutions all over the nation and the world. "I believe sharing resources is important for science and medicine to advance," says Dr. Wu.
The HECTOR trial evaluates new treatments for heart failure
For decades, Dr. Wu has pioneered groundbreaking research at Stanford Medicine. Currently, he is the principal investigator for a clinical trial that studies the use of human embryonic stem cell-derived cardiomyocytes (hESC-CMs) to prevent heart failure and treat patients with the condition.
The trial is called "Human Embryonic Stem Cell-Derived Cardiomyocytes in PaTients with ChrOnic Ischemic Left VentRicular Dysfunction Secondary to Myocardial Infarction (HECTOR)." The study focuses on patients who are at risk of heart failure from chronic ischemic cardiomyopathy.
It is the first in-human study in the U.S. that evaluates the use of hESC-CMs to treat heart failure. The HECTOR trial reflects Dr. Wu’s passion for discovering breakthrough treatments and his commitment to shaping the future of cardiovascular care.
Learn more about Dr. Wu’s vision for cellular therapy and precision medicine
To hear Dr. Wu explain his work and research, watch his 2023 AHA presidential address. Learn more about Dr. Wu, including his many awards, publications, and clinical interests.