Ep. 317: “Engineering the Human Heart” Featuring Dr. Aitor Aguirre
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In this episode of The Stem Cell Podcast, hosts Dr. Dalen James and Dr. Arun Sharma welcome Dr. Aitor Aguirre from Michigan State University to discuss his pioneering work in engineering human heart models using pluripotent stem cells and advanced organoid technologies. The episode begins with a roundup of recent stem cell research, including a human cerebral organoid model of West Nile virus encephalitis that revealed intrinsic innate immune responses despite lacking a full immune system, a high-throughput drug repurposing screen identifying sildenafil (Viagra) as a promising treatment for Leigh syndrome, and a patient-derived organoid study uncovering transcription factor-driven epigenetic remodeling in breast cancer metastasis. These stories highlight the growing power of stem cell models in infectious disease, mitochondrial disorders, and cancer. The core of the episode centers on Dr. Aguirre’s lab, which focuses on developing biomimetic heart organoids and assembloids that incorporate immune cells (macrophages) and neural crest cells to better model cardiac development, arrhythmias like atrial fibrillation, and the brain-heart axis. Aguirre emphasizes the synergy between bioengineering and self-organization, advocating for an engineering mindset that leverages cellular autonomy while improving control and instrumentation. He also shares insights on the value of preprints, the importance of collaboration, and his personal passion for astronomy. The episode closes with reflections on the evolving nature of scientific discovery, teamwork, and the profound questions about the origins of life and the universe.
Sildenafil (Viagra), a drug originally developed for erectile dysfunction, shows promise in treating Leigh syndrome by rescuing mitochondrial dysfunction in patient-derived organoids and improving muscle strength and metabolic resilience in patients.
Heart organoids incorporating immune cells (macrophages) and neural crest cells enable more physiologically relevant modeling of cardiac development, arrhythmias, and neuro-immune interactions, opening new avenues for disease modeling and drug screening.
The integration of engineering principles with self-organizing biological systems—such as using bioengineering to create environments that guide, rather than dictate, cellular organization—represents a powerful hybrid approach in regenerative medicine.
Preprints on bioRxiv allow early dissemination of science, accelerate feedback, and can generate significant impact even before formal publication, especially when supported by rigorous data and collaboration.
Successful scientific innovation increasingly relies on interdisciplinary teamwork, where diverse expertise—from cardiology and immunology to neuroscience and bioengineering—converges to tackle complex biological questions.
Introduction and Episode Overview
The hosts introduce the episode, welcome Dr. Aitor Aguirre from Michigan State University, and preview the topics: a roundup of recent stem cell research on West Nile virus, Leigh syndrome, and breast cancer, followed by an in-depth discussion on heart organoid and assembloid technology.
West Nile Virus in Human Cerebral Organoids
“I thought it was really cool that not only they elucidated this kind of neural intrinsic viral response that can clear, but then showed and even in long term infection that there are targets that could, you know, you could deploy existing or new methods to staunch that encephalitis and subsequent effects.”
Drug Repurposing for Leigh Syndrome with Sildenafil
“This is an odyssey of a drug that was meant for one thing, ultimately changed the world literally toward another effect and now has swung back to something that is much more clinically focused rather than recreational.”
Epigenetic Profiling of Breast Cancer with Patient-Derived Organoids
A deep omics analysis of patient-derived organoids revealed transcription factor-driven epigenetic remodeling linked to breast cancer metastasis. The study identified druggable targets and demonstrated that depleting specific transcription factors impaired spontaneous metastasis in vivo.
Basic Science: Plasticity in Aseel Worm Development
The hosts discuss a study on the aseel worm (H. miamiya), which exhibits an invariant cleavage program but unexpectedly high developmental plasticity. Single macromeres can regenerate a full organism, challenging assumptions about early cell fate restriction and underscoring the value of basic developmental biology.
“This is an odyssey of a drug that was meant for one thing, ultimately changed the world literally toward another effect and now has swung back to something that is much more clinically focused rather than recreational.”
“I thought it was really cool that not only they elucidated this kind of neural intrinsic viral response that can clear, but then showed and even in long term infection that there are targets that could, you know, you could deploy existing or new methods to staunch that encephalitis and subsequent effects.”
“I would like to know more about you know, the origins of the universe perhaps what are we really doing here? I think that's the basic question where does everything come from.”
Hosts
Guest
Aitor Aguirre
person
West Nile virus
other
Dalen James
person
Arun Sharma
person
Leigh syndrome
other
sildenafil
product
Michigan State University
organization
breast cancer
other
bioRxiv
other
James Webb Space Telescope
other
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