Prof. Terry Hébert and Giada Castagnola
Photo Credit: Owen Egan / Joni Dufour.
Scientific Frontline: Extended "At a Glance" Summary: "Heart-in-a-Dish" Technology for Dilated Cardiomyopathy
The Core Concept: Researchers have developed an in vitro model that reprograms a patient's blood cells into stem cells, and subsequently into genetically identical heart muscle cells, to simulate heart disease.
Key Distinction/Mechanism: Unlike conventional one-size-fits-all treatments, this approach combines human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) with advanced microscopy to evaluate the signaling and functional landscape at the single-cell level, identifying patient-specific physiological differences.
Major Frameworks/Components:
- Cellular reprogramming of blood samples into functional, miniature beating heart tissues.
- Single-cell microscopic evaluation of cardiomyocyte physiology.
- Comparative analysis of sex-based hormonal responses in failing heart tissue.
Branches of Science: Cardiology, Stem Cell Biology, Pharmacology, and Molecular Genetics.
Future Application: Expanding the model to larger cohorts to develop highly personalized therapeutic targets, uncover sex-based biological differences in heart disease, and move beyond standard heart failure treatments.
Why It Matters: Dilated cardiomyopathy exhibits an approximate fifty percent five-year mortality rate; identifying patient-specific responses to therapeutics could fundamentally alter survival outcomes and standard cardiological care.
McGill researchers have developed a new way to study why the same heart failure treatment can help some patients recover while others continue to get worse.
Combining “heart-in-a-dish” technology with advanced microscopy, the approach makes it possible to identify differences between patients that would likely be missed using conventional methods.
The pilot study helps pave the way for more personalized treatment for dilated cardiomyopathy, a serious form of heart disease. Only about half of patients survive five years after diagnosis. Despite major differences in how the disease progresses, patients typically receive the same standard treatments.
“We finally have tools that can help us move beyond a one-size-fits-all approach to heart failure,” said senior author Terry Hébert, professor in McGill University's Department of Pharmacology and Therapeutics.
From blood sample to beating heart
Heart-in-a-dish technology begins with a blood sample. Researchers reprogram blood cells into stem cells and then transform them into heart muscle cells carrying the patient's genetic makeup. Those cells are assembled into miniature beating heart tissues that allow scientists to simulate the disease in the lab and test potential treatments.
For this study, the team used cells from two patients with dilated cardiomyopathy and two healthy volunteers. A powerful microscope installed at McGill in 2024 made it possible to study the miniature hearts at the individual cell level.
The study was co-led by Giada Castagnola and Diego Loggia, PhD students in McGill's Department of Pharmacology and Therapeutics, along with colleagues at McGill and the Research Institute of the McGill University Health Centre.
Notably, they found that cells from the female patient responded to a hormone that was not expected to improve heart function. The response was not seen in the male patient or healthy volunteers.
“This is exactly the kind of difference we hope to uncover,” said Hébert. “While preliminary, the finding suggests a potential therapeutic target and could help improve our understanding of differences in heart disease between women and men that have long been understudied.”
The team is now expanding the study, with heart cells already grown from samples collected from 40 people.
“As we expand this work to more patients, we expect to uncover biological differences that could ultimately change how heart failure is treated,” said Hébert.
Published in journal: npj Biomedical Innovations
Authors: Giada Castagnola, Diego Loggia, Kyla Bourque, Karima Alim, Ida Derish, Elise Rody, Zosia Gryz, Cara Hawey, Jace Jones-Tabah, Anjali Bhardwaj, Ludovic Mouttet, Natalie Gendron, Nadia Giannetti, Renzo Cecere, Sonya K. Hui, and Terence E. Hébert
Source/Credit: McGill University
Edited by: Scientific Frontline
Reference Number: bio110226_01
