First mature human heart muscle grown from patient-specific stem cells
Scientists have grown the first human heart muscle that functions just like an adult’s would.
Instead of the nine months it takes for a baby’s heart to develop in the womb, they grew a functioning heart from stem cells in just four weeks.
Although researchers can grow many tissues, including the heart muscle, from stem cells, scientists at Columbia University were able to build one mature enough to be useful for medical research for the first time.
This development is a step forward in studying human physiology as it gives researchers a way to test treatments for conditions like heart failure on a lab-grown heart that can mimic a diseased adult one.
This is not the first time scientists have managed to grow a heart muscle, but senior author Dr. Gordana Vunjak-Novakovic said those cardiac tissues have failed to mimic or show some of the critical hallmarks of an adult human heart, like it’s tissue structure and beat pattern.
Their findings are published in journal Nature.
Professor of medicine at Columbia University Vagelos College of Physicians and Surgeons, Dr. Vunjak-Novakovic, said: “Many of the ongoing efforts including those from our lab have been biomimetic in nature, trying to recapitulate the known events present during native development.”
“The common approach in our field has been that the more mature the starting cardiomyocytes, the better,” said her fellow researcher Dr Kacey Ronaldson-Bouchard.
“Because these efforts have been limited in how much maturation can be achieved, we decided to try something totally new: to explore the concept of accelerated development,” she added.
The conventional wisdom for growing stem cell-based organs is to use cells in a later stage of development so that they are closer to specializing into the kind of tissue the scientists wish to study.
But in growing their new heart, the Columbia researchers tried a different and bold method.
In other words, they used very early-stage stem cells, which were easier to manipulate and, they hoped, would respond better to stimulation intended to accelerate their growth.
To speed up the development of the heart tissues, the researchers delivered electric pulses to the heart to stimulate it enough to make it twitch, which is exactly what happens in healthy heart muscle in the body.
“We found that very early-stage cells, which still have developmental plasticity, would respond better to the external signals we deliver to drive maturation,” said Dr. Ronaldson-Bouchard.
Scientists were also able to develop the methods and software to measure the frequency, amplitude, force of contractions, and its responses to drugs.
This breakthrough also enables them to manipulate the cardiac tissue to make it behave like a diseased heart so that they can further research life-threatening conditions impacting the organ as well as its response to certain drugs.
Instead of relying on the spontaneous pulse of a developing fetal heart, Dr. Vunjak-Novakovic and her colleagues used a special method of electromechanical conditioning in which they increased the frequency of electrically induced contractions little by little every day.
Researchers believe this practice forced the bioengineered heart to mature rapidly.
Within four weeks, the stem cells had taken on the shape of adult heart cells, and were starting to function like them, too.
Dr. Vunjak-Novakovic and her team aren’t the only ones using stem cells to research, treat and cure diseases.
Earlier this year, doctors have declared that stem cell transplants are a ‘game changer’ for millions of people suffering from multiple sclerosis, a disabling disease of the brain and spinal cord, after a 100 patients trial done at Northwestern University showed that the method was able to stop the debilitating disease in its tracks
In the current study, Vunjak-Novakovic’s team plan to use the mature human heart muscle to mimic the observable characteristics of some heart conditions to get a better understanding of cardiac disease and cardiotoxicity induced by drugs used to treat other organ systems.
“The resulting engineered tissue is truly unprecedented in its similarity to functioning human tissue,” said Seila Selimovic, director of the NIBIB (National Institute of Biomedical Imaging and Bioengineering) Tissue Chips program, within the National Institutes of Health that funded this research.
“The ability to develop mature cardiac tissue in such a short time is an important step in moving us closer to having reliable human tissue models for drug testing.”