The Beating Heart in a Dish
How Joseph Wu's Stem Cell Research is Revolutionizing Medicine
In a Stanford laboratory, heart cells derived from a simple blood sample hold the key to personalized medicine and the future of drug development.
Imagine a future where your medication is tailored not just to your disease, but to your unique genetic makeup. Where doctors test treatments on your own cells in a lab dish before prescribing them to you. This isn't science fiction—it's the groundbreaking work of Dr. Joseph C. Wu, who transforms ordinary blood cells into living, beating human heart tissue to revolutionize how we understand and treat disease. Through his innovative use of induced pluripotent stem cells, Dr. Wu is bringing us closer to a new era of personalized medicine.
From Taiwanese Immigrant to Scientific Visionary
Education
MD from Yale School of Medicine, PhD from UCLA in molecular and medical pharmacology 1
Honors
Presidential Early Career Award presented by President Obama 1
Leadership
President of American Heart Association (2023-2024) 1
Joseph Wu's journey to becoming one of the most influential cardiovascular researchers began far from the laboratories of Stanford. His family fled Taiwan when he was nine years old, eventually settling in Los Angeles where his father worked as a farmer in California's Central Valley 5 . The young Wu initially dreamed of becoming an astronaut, fascinated by the night sky he observed while helping on the farm. Though nearsightedness eventually dashed those dreams, he redirected his curiosity toward science and medicine 5 .
Dr. Wu's career path reflects his interdisciplinary approach to science. He earned his medical degree from Yale School of Medicine in 1997, then returned to UCLA for his medicine internship, residency, cardiology fellowship, and a PhD in molecular and medical pharmacology 1 . Under the mentorship of the late Dr. Sanjiv Sam Gambhir, who pioneered revolutionary molecular imaging techniques, Wu found his calling in cardiovascular research 5 .
The Stem Cell Revolution: From Skin Cells to Beating Hearts
At the core of Dr. Wu's revolutionary research are induced pluripotent stem cells (iPSCs)—ordinary adult cells (typically from blood or skin) that have been reprogrammed back into an embryonic-like state, capable of becoming any cell type in the body 5 . This technology, pioneered by Shinya Yamanaka who won the Nobel Prize for this discovery in 2012, provides an endless supply of patient-specific cells for research and potential therapies.
Beating heart cells created from iPSCs
Applications of iPSC Technology in Cardiovascular Research
| Application Area | Description | Impact |
|---|---|---|
| Disease Modeling | Creating patient-specific heart cells with inherited conditions like cardiomyopathies and channelopathies | Enables study of disease mechanisms and genotype-phenotype correlations 2 |
| Drug Discovery | Testing drug efficacy and safety on human heart cells before human trials | Identifies toxic compounds early; accelerates development timeline 2 |
| Personalized Medicine | Using patient-specific cells to identify most effective medications | Moves beyond "one-drug-fits-all" to tailored treatments |
| Regenerative Medicine | Developing stem cell-derived cardiomyocytes for heart repair | Potential future therapy for heart failure patients 2 4 |
Clinical Trial in a Dish: The Future of Drug Testing
One of Dr. Wu's most innovative concepts is the "clinical trial in a dish" approach, which could dramatically accelerate and improve drug development 1 . The current process for bringing a new drug to market takes approximately 12 years and costs over $1.8 billion on average 2 . Worse, many drugs fail late in development due to unexpected heart toxicity—a problem Dr. Wu's research aims to solve.
Current Drug Testing
"One of the most common causes for drugs being withdrawn post-marketing is because of cardiotoxicity," Dr. Wu explains . Currently, pharmaceutical companies primarily test for heart toxicity using engineered cell lines like Chinese Hamster Ovary (CHO) cells that express only a single human ion channel (hERG). This limited model produces both false positives and false negatives—sometimes with dangerous consequences .
iPSC Solution
Dr. Wu illustrates this problem with the example of verapamil, a common blood pressure medication: "If you test verapamil on CHO cells, the results will say that it's toxic because it is only measuring the hERG blocking effect. But it is quite safe in patient-specific iPS cells that we've tested in our lab because these cells have more than just the hERG channel" .
The solution? Using comprehensive human iPSC-derived cardiomyocytes that contain all the relevant ion channels present in actual human heart cells.
Drug Development Process Improvement
A Journey Into Space: The NASA Cardiac Study
When NASA wanted to study how space travel affects human heart health, they turned to Dr. Wu's lab—bringing his childhood astronaut dreams full circle 5 . His team designed a series of elegant experiments sending stem cell-derived heart tissues into space to study the effects of microgravity and cosmic radiation.
2016 Experiment
In their initial experiment, researchers sent two-dimensional iPSC-derived cardiomyocytes to the International Space Station while maintaining identical cells on Earth as controls. They discovered that the cardiomyocytes in space displayed altered metabolism and contractability 5 .
2020 Research
The research progressed to more advanced three-dimensional cardiac organoids, with similar results confirming earlier 2D findings in more physiologically relevant 3D models 5 .
2023 Mission
In their most ambitious space experiment in 2023, the team sent 3,800 iPSC-derived cardiac organoids into orbit, with half treated with a candidate medication to potentially counteract the observed space-induced changes 5 .
Key Findings from NASA Studies
- Cardiomyocytes in space show altered metabolism
- Contractility changes in microgravity
- 3D models confirm 2D findings
- Potential protective drugs being tested
International Space Station where cardiac experiments were conducted
Measuring the Beat: A Key Experiment Unveiled
To understand how Dr. Wu's team studies heart cells, let's examine a key experimental protocol from their research—a method to simultaneously measure contraction, calcium handling, and action potential in iPSC-derived cardiomyocytes 3 .
Step-by-Step Experimental Protocol
1. Cell Preparation
Researchers first differentiate human iPSCs into beating cardiomyocytes using specific chemical signals that mimic natural heart development. These cells are plated on specialized dishes compatible with imaging systems.
2. Fluorescent Labeling
The team uses fluorescent dyes that change their light emission properties in response to specific cellular events. Different dyes are selected to track calcium fluctuations and electrical activity separately.
3. Simultaneous Measurement
Using advanced microscopy, researchers capture high-speed videos of the beating cells while recording the fluorescent signals from the dyes. This allows them to correlate mechanical contraction with underlying calcium and electrical changes.
4. Data Analysis
Specialized software analyzes the recorded signals to extract key parameters including contraction strength, calcium transient duration, and action potential morphology—all critical indicators of heart cell health and function.
Key Measurements
Contractile Function
Force and pattern of cell contraction. Detects drugs that may weaken heart muscle or cause arrhythmias.
Calcium Handling
How calcium ions are managed within the cell. Identifies compounds that disrupt calcium cycling essential for coordinated beats.
Action Potential
Electrical signaling that triggers contraction. Flags drugs that cause dangerous heart rhythm disturbances.
The Scientist's Toolkit: Essential Research Reagents
Dr. Wu's research relies on sophisticated laboratory tools and reagents that enable the precise manipulation and study of stem cells. Here are some key components of their experimental toolkit:
mTeSR™1 Medium
A defined, feeder-free culture medium that allows human pluripotent stem cells to grow reliably without mouse feeder cells. Dr. Wu's lab has used this medium for over five years, noting that "mTeSR™1 was the first defined media which allowed us to grow human pluripotent stem cells in a more reliable way" .
CRISPR/Cas9 Genome Editing
This powerful gene editing technology allows researchers to introduce specific disease-causing mutations into healthy cells or correct mutations in patient-derived cells. This enables precise study of how individual genetic changes affect heart cell function 2 .
Multielectrode Array Systems
These devices measure the electrical activity of cardiac cells and tissues, providing crucial information about heart rhythm and detecting arrhythmias caused by drugs or genetic conditions 7 .
Molecular Imaging Probes
Adapted from Dr. Wu's training with Dr. Gambhir, these include specialized fluorescent and bioluminescent markers that allow non-invasive tracking of cell survival, integration, and function after transplantation 2 .
Differentiation Kits
Commercial reagent systems that provide specific growth factors and signaling molecules to direct stem cells to become functional cardiomyocytes with high efficiency and consistency.
From Lab Bench to Hospital Bed: The Future of Medicine
The implications of Dr. Wu's work extend far beyond basic research. His team is currently leading the HECTOR trial—a first-in-human study evaluating the safety of human embryonic stem cell-derived cardiomyocytes for treating heart failure 4 6 . This phase I clinical trial represents a crucial step toward potentially regenerative therapies for patients with chronic ischemic left ventricular dysfunction.
Vision for Personalized Medicine
"I am a firm believer that 10 to 20 years from now, we should be able to draw blood, make iPS cells, differentiate them into cardiac cells or other cell types, and expose these cells to different drugs to find out what would be the ideal drug for that patient" .
Impact on Medical Practice
This vision of personalized medicine could eliminate much of the guesswork from prescribing medications, particularly for complex conditions where patient response varies significantly. Instead of trying multiple drugs sequentially—the current "hit-or-miss approach"—doctors could first identify the optimal treatment using the patient's own cells in the laboratory .
As Dr. Wu assumes leadership roles including the presidency of the American Heart Association, he remains focused on his core mission: "I want to raise public awareness about the importance of cardiovascular health because heart disease is the number one cause of mortality... and [emphasize] the importance of investing in biomedical research that will benefit our patients in the future" 5 .
Through his innovative integration of stem cell biology, genomics, artificial intelligence, and drug discovery, Dr. Joseph Wu is not just studying the beating heart—he's redefining the future of medicine itself, one cell at a time.