TORONTO, ON – Researchers at the University of Toronto’s Institute of Biomaterials & Biomedical Engineering (IBBME) and the McEwen Centre for Regenerative Medicine have identified the optimal structure and cell ratio associated with heart function – and the discovery has already led the team to another research first: the engineering of the first-ever living, three-dimensional human arrhythmic tissue. The team’s foundational study will be published in this week’s biomedical journal PNAS (Proceedings of the National Academy of Science).
The study marks the first time that researchers have tried to define and formulate the precise type and ratio of cell types that produce highly functional cardiac tissue.
“Hearts are not just composed of one type of cell,” explained fourth-year IBBME PhD Student Nimalan Thavandiran and first author of the PNAS study. But until now, scientists have not known how to mix different cell types in engineered heart tissue in such a way that the tissue achieves the composition and maturity level of the native human heart.
Thavandiran solved this mystery by methodically separating different cell types derived from human pluripotent stem cells and precisely mixing them back together. Using scoring metrics associated with functional hearts – contraction, electrical activity and cell alignment – Thavandiran was able to develop a formula for engineering highly functional heart tissue.
“The composition of the cells is vital,” stated Thavandiran. “We discovered that a mixture of 25% cardiac fibroblasts (skin-like cells) to 75% cardiomyoctes (heart cells) worked best.” The carefully composed cell ratios were then grown in three-dimensional “wires” that mimic the structure of human heart tissue.
“An exciting result of our study is our ability to miniaturize the tissues into human heart micro-tissues that can be used to measure normal and diseased human heart responses to drugs,” emphasized Professor Peter Zandstra, corresponding author of the study and Canada Research Chair in Stem Cell Bioengineering at IBBME and the McEwen Centre for Regenerative Medicine.
From discovering the right composition of heart cells, the researchers next designed the first-ever three-dimensional arrhythmia tissue model. Since human heart cells aren’t easily grown, being able to engineer highly functional heart tissue from human stem cells is a vital concern for cardiac researchers.
Millions of people experience arrhythmia each year, a condition in which the feedback of electrical pulses of the heart is interrupted, leaving the heart unable to contract and pump blood effectively.
With the right cellular composition, the researchers engineered the circular tissue model associated with arrhythmia. The team then applied electrical pulses to the arrhythmic tissues, ‘zapping’ the irregularly beating tissue into a state of regular contractions.
The University of Toronto’s Institute of Biomaterials & Biomedical Engineering (IBBME) is a unique, multidisciplinary graduate research unit at the at the cutting edge of innovation in biomedical engineering – where investigators from the faculties of engineering, medicine and dentistry collaborate to find innovative solutions to the world’s most pressing health care challenges.
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