Nav: Home

Bioengineered human cardiac models spur disruptive innovation in disease research

October 24, 2018

TORONTO (23 Oct. 2018) -- Thrombosis-on-a-chip, vasculature-on-a-chip and engineered models of human cardiac fibrosis are just a few of the new technologies revolutionizing research into human cardiovascular disease--a condition responsible for 17 million deaths per annum globally. A new study entitled Cardiovascular Disease Models: A Game Changing Paradigm in Drug Discovery and Screening, published this week in the journal Biomaterials by bioengineering scientists from the University of Toronto, proposes a new paradigm for research into cardiovascular diseases. The new paradigm is rooted in a human-specific understanding of disease mechanisms, coupled with application of novel microphysiological and computational tools based on human biology to create more predictive laboratory models of the human disease.

Lead author, Dr. Houman Savoji, CIHR & FRQNT postdoctoral fellow in Prof. Milica Radisic's Laboratory, explained that, "In vitro and in silico disease models are frequently used to complement or confirm data acquired from animal models. However it is apparent that the application of these two fast-growing and emerging platforms, given their reduced costs, more ethical and more accurate, human-relevant outcomes, are becoming promising substitutes for animal models. The development of multi-functional platforms that combine mechanistic knowledge about the pathophysiology and etiology of cardiovascular diseases with ever-expanding engineering technologies (i.e., micro/nanofabrication) and advances in stem cell biology, brings hope to the mandate of improving translation in drug discovery and concomitantly reducing the use of experimental animals in preclinical research."

The cardiovascular system is one of the most complex human systems to model, given its intimate functional interactions with the vasculature, nervous and renal systems. Traditionally, animals have been used for this purpose; however, animal models of cardiac disease may not show all the features of a specific condition, and even genetically modified animals cannot recapitulate human cardiovascular disease. There are difficulties in translating information from animal models to the human situation -- even for healthy heart function -- due to the enormous differences in heart size, architecture, rate of beating, oxygen consumption, contractility, protein expression and stem cell populations between mice and humans. Dr. Savoji describes how "not all experimental models (i.e., mice and rats) are acceptable for [studying] atherosclerosis due to intrinsic genetic differences, and their [the animals'] higher resistance to...high cholesterol diet."

The exciting advances detailed in Dr. Savoji's paper offer suggestions for improving and further developing current models of the heart and cardiovascular system. Electrical stimulation can be applied to stem cell models to promote cellular maturity, creating models that more closely resemble an adult heart; multi-dimensional scaffolds with in-built vascular networks start to mirror the complexity of the cardiovascular system; mechanistic and data-driven modelling (using quantitative systems pharmacology or QSP) inform dose selection, drug-drug interaction and ultimately, identification of the best therapeutic strategy. Coupling these approaches with the use of patient-derived stem cells to create bespoke disease models will create more reliable, predictive models for disease onset, progression and drug response.

The need for such a new approach is evidenced by the high failure rates of drugs in general, and by the severity of adverse drug reactions in late-stage clinical development as a result of cardiovascular toxicity. For example, Vioxx (Rofecoxib), originally designed to treat pain related to osteoarthritis and approved by the U.S. Food and Drug Administration in 1999, was linked to over 27,000 cardiovascular-related deaths, and doubled the risk of heart attack and stroke. Vioxx was withdrawn from the market in 2004. Recent developments in computational and mechanistic cardiac modelling have opened new avenues to improve predictions of drug-induced cardiotoxicity before these drugs are released into the clinic.
-end-
The review by Savoji et al. was supported with funding from Humane Society International and the Humane Society of the United States on behalf of the BioMed21 Collaboration.

Humane Society International

Related Cardiovascular Articles:

Framework on how to safely resume essential cardiovascular diagnostic and treatment care during the COVID-19 pandemic, from the AHA and 14 North American cardiovascular societies
The American Heart Association, together with 14 cardiovascular societies in North America, today issued joint guidance, 'Safe Reintroduction of Cardiovascular Services during the COVID-19 Pandemic: Guidance from North American Society Leadership,' to outline a systematic, phased approach to safely reintroducing cardiovascular procedures for diagnosis and treatment during the COVID-19 pandemic.
Cardiovascular impairment in COVID-19
Anti-inflammatory therapies should be used to treat COVID-19 patients that are at risk of, or have developed, cardiovascular problems, recommend leading cardiologists from Beijing, China, who have detailed the different ways that COVID-19 could trigger serious inflammatory-related cardiovascular issues in patients.
A talk with your GP may prevent cardiovascular disease
Having a general practitioner (GP) who is trained in motivational interviewing may reduce your risk of getting cardiovascular disease.
Improving cardiovascular health of the most vulnerable
A two-year pilot project led by Rick Stouffer, MD, shows how the cardiovascular health of the most vulnerable patients can be improved with free medications.
New insights into the effect of aging on cardiovascular disease
Aging adults are more likely to have - and die from - cardiovascular disease than their younger counterparts.
Aspirin may no longer be effective as cardiovascular treatment
A new paper in Family Practice, published by Oxford University Press, found that the widespread use of statins and cancer screening technology may have altered the benefits of aspirin use.
Premature death from cardiovascular disease
National data were used to examine changes from 2000 to 2015 in premature death (ages 25 to 64) from cardiovascular disease in the United States.
Study identifies cardiovascular toxicities associated with ibrutinib
After a recent study showed that chronic lymphocytic leukemia patients who received ibrutinib as a frontline treatment had a 7% death rate, a new study offers a clearer picture on the reasons for the deaths.
Vitamin D supplementation not associated with reduced cardiovascular events
This study, called a meta-analysis, combined the results of 21 randomized clinical trials with about 83,000 patients to look at whether vitamin D supplementation was associated with reduced risk of cardiovascular disease events such as heart attack or stroke.
Medicaid expansion associated with fewer cardiovascular deaths
Expanding Medicaid eligibility was associated with lower rates of death from cardiovascular causes in a study comparing data from counties in 29 states that expanded Medicaid with 19 states that didn't from 2010 to 2016.
More Cardiovascular News and Cardiovascular Current Events

Trending Science News

Current Coronavirus (COVID-19) News

Top Science Podcasts

We have hand picked the top science podcasts of 2020.
Now Playing: TED Radio Hour

Listen Again: Reinvention
Change is hard, but it's also an opportunity to discover and reimagine what you thought you knew. From our economy, to music, to even ourselves–this hour TED speakers explore the power of reinvention. Guests include OK Go lead singer Damian Kulash Jr., former college gymnastics coach Valorie Kondos Field, Stockton Mayor Michael Tubbs, and entrepreneur Nick Hanauer.
Now Playing: Science for the People

#562 Superbug to Bedside
By now we're all good and scared about antibiotic resistance, one of the many things coming to get us all. But there's good news, sort of. News antibiotics are coming out! How do they get tested? What does that kind of a trial look like and how does it happen? Host Bethany Brookeshire talks with Matt McCarthy, author of "Superbugs: The Race to Stop an Epidemic", about the ins and outs of testing a new antibiotic in the hospital.
Now Playing: Radiolab

Speedy Beet
There are few musical moments more well-worn than the first four notes of Beethoven's Fifth Symphony. But in this short, we find out that Beethoven might have made a last-ditch effort to keep his music from ever feeling familiar, to keep pushing his listeners to a kind of psychological limit. Big thanks to our Brooklyn Philharmonic musicians: Deborah Buck and Suzy Perelman on violin, Arash Amini on cello, and Ah Ling Neu on viola. And check out The First Four Notes, Matthew Guerrieri's book on Beethoven's Fifth. Support Radiolab today at Radiolab.org/donate.