Early stimulation improves performance of bioengineered human heart cells

Researchers from Columbia University, New York City, are now able to use induced pluripotent stem cells (iPSC) to form a model of human adult-like cardiac muscle by introducing electric and mechanical stimulation at an early stage. Since this muscle is similar to the adult heart, it could serve as a better model for testing the effects of drugs and toxic substances than current tissue-engineered heart models.

The iPS-derived cardiomyocytes have formed heart tissue that closely mimics human heart functionality at over four weeks of maturation. Image credit: Columbia University

Stem cells have the potential to turn into many different types of cells. Human cells lose this flexibility once they have matured, which is why, for example, heart cells don’t spontaneously decide to become lung cells. iPSCs are cells taken from an adult that have been manipulated, or induced, into a stem-cell state.

Researchers are then able to guide these “blank slate” cells into different cell types by using various chemical and physical stimuli. Scientists have been able to engineer cardiac tissue using iPS-derived cardiomyocytes (iPS-CMs) for years.

However, engineering tissue that can successfully mimic the intricacies of adult human heart cells is not easy and, until now, had not been achieved in the lab.

They have made significant strides in reliably engineering human heart muscle that mimics adult myocardium. They found that the longer they waited to introduce physical stimuli such as electric current and mechanical stimulation to the iPSCs, the less responsive the cells were. The team reasoned that the earlier they introduced electromechanical stimuli, the greater the effect would be.

They tested two types of iPS-CMs: early stage (12-day old cells) and late stage (28-day old mature cells) under three different scenarios.

The first test condition was a control in which there was no stimulation whatsoever. The second was three weeks of constant electrical stimulation. The third was two weeks of progressively increasing levels of electrical stimulation followed by a week of constant intensity stimulation. This third scenario mimicked the changes the human heart undergoes during the last few weeks of fetal development and after birth.

The researchers found that the third scenario, introducing physical conditioning at an increasing intensity to early stage iPS-CMs, helped them form adult-like human cardiac tissue after just four weeks of culture in the lab.

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. (National Institutes of Health)

YOU MAY ALSO LIKE

Physical Activity May Reduce Age-Related Movement Problems

Age-related brain lesions known as white matter hyperintensities have been linked to movement problems and disabilities later in life. These lesions, which appear as bright spots on MRI images, can be used as a proxy measure of brain white matter disease. They are thought to reflect small blood vessel disease, and have also have been associated with dementia and other health issues in older people.

New Test May Detect Pancreatic Cancer Early

Researchers have developed a blood test that could help with the early detection of pancreatic cancer, one of the deadliest forms of the disease.

Few people with peanut allergy tolerate peanut after stopping oral immunotherapy

Allergy to peanut, which is often severe, is one of the most common food allergies. Although previous studies have shown that peanut oral immunotherapy (OIT) — ingesting small, controlled amounts of peanut protein —can desensitize adults and children and prevent life-threatening allergic reactions, the optimal duration and dose is unknown.

Disrupting the gut microbiome may affect some immune responses to flu vaccination

Researchers from Stanford University found that oral antibiotics, which can kill gut microorganisms, can alter the human immune response to seasonal influenza vaccination.

Nanoparticles used to transport anti-cancer agent to cells

Scientists from the University of Cambridge have developed a platform that uses nanoparticles known as metal-organic frameworks to deliver a promising anti-cancer agent to cells.

The brain may actively forget during dream sleep

Rapid eye movement, or REM, sleep is a fascinating period when most of our dreams are made. Now, in a study of mice, a team of Japanese and U.S. researchers show that it may also be a time when the brain actively forgets.