What composes the human heart? Researchers crunch the numbers

Nov 20, 2013 by Erin Vollick

A foundational study published in the journal PNAS (Proceedings of the National Academy of Sciences) this week by 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 study marks the first time that researchers have tried to define and formulate the precise type and ratio of that produce highly functional cardiac .

"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 in such a way that the tissue achieves the composition and maturity level of the native .

Thavandiran solved this mystery by methodically separating out different cell types derived from human pluripotent stem 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.

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, though, the researchers were able to engineer 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.

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.

"We can now combine this compositional knowledge with electrical stimulation and mechanical stimulation to obtain a truly biomimetic system necessary for cardiac research," cited corresponding author Associate Professor Milica Radisic, core faculty at IBBME and the Department of Chemical Engineering and Applied Science, and Canada Research Chair in Functional Cardiovascular Tissue Engineering.

Stressing the urgent need for highly functional tissue to perform important drug screening research, Thavandiran added, "We're making a really big push to bring this model to the marketplace."

The team has been working with the Centre for the Commercialization of Regenerative Medicine (CCRM) to commercialize their tissue modeling platform.

Explore further: Researchers develop spring-like fibers to help repair damaged heart tissue

More information: Design and formulation of functional pluripotent stem cell-derived cardiac microtissues, www.pnas.org/cgi/doi/10.1073/pnas.1311120110

Related Stories

Scientists build a living patch for damaged hearts

May 06, 2013

Duke University biomedical engineers have grown three-dimensional human heart muscle that acts just like natural tissue. This advancement could be important in treating heart attack patients or in serving as a platform for ...

Hybrid heart valve is strong, durable in early tests

Nov 18, 2013

A hybrid heart valve created from thin and highly elastic mesh embedded within layers of human cells was strong and durable in a study presented at the American Heart Association's Scientific Sessions 2013.

Predicting the fate of stem cells

Oct 22, 2013

University of Toronto researchers have developed a method that can rapidly screen human stem cells and better control what they will turn into. The technology could have potential use in regenerative medicine and drug development. ...

Recommended for you

Researchers successfully clone adult human stem cells

Apr 18, 2014

(Phys.org) —An international team of researchers, led by Robert Lanza, of Advanced Cell Technology, has announced that they have performed the first successful cloning of adult human skin cells into stem ...

Researchers develop new model of cellular movement

Apr 18, 2014

(Phys.org) —Cell movement plays an important role in a host of biological functions from embryonic development to repairing wounded tissue. It also enables cancer cells to break free from their sites of ...

For resetting circadian rhythms, neural cooperation is key

Apr 17, 2014

Fruit flies are pretty predictable when it comes to scheduling their days, with peaks of activity at dawn and dusk and rest times in between. Now, researchers reporting in the Cell Press journal Cell Reports on April 17th h ...

User comments : 0

More news stories

Biologists help solve fungi mysteries

(Phys.org) —A new genetic analysis revealing the previously unknown biodiversity and distribution of thousands of fungi in North America might also reveal a previously underappreciated contributor to climate ...

Researchers successfully clone adult human stem cells

(Phys.org) —An international team of researchers, led by Robert Lanza, of Advanced Cell Technology, has announced that they have performed the first successful cloning of adult human skin cells into stem ...

NASA's space station Robonaut finally getting legs

Robonaut, the first out-of-this-world humanoid, is finally getting its space legs. For three years, Robonaut has had to manage from the waist up. This new pair of legs means the experimental robot—now stuck ...

Ex-Apple chief plans mobile phone for India

Former Apple chief executive John Sculley, whose marketing skills helped bring the personal computer to desktops worldwide, says he plans to launch a mobile phone in India to exploit its still largely untapped ...

Filipino tests negative for Middle East virus

A Filipino nurse who tested positive for the Middle East virus has been found free of infection in a subsequent examination after he returned home, Philippine health officials said Saturday.

Egypt archaeologists find ancient writer's tomb

Egypt's minister of antiquities says a team of Spanish archaeologists has discovered two tombs in the southern part of the country, one of them belonging to a writer and containing a trove of artifacts including reed pens ...

Airbnb rental site raises $450 mn

Online lodging listings website Airbnb inked a $450 million funding deal with investors led by TPG, a source close to the matter said Friday.