БиоПро Выбор потребителя 2018 #06

New method will help stem cells to efficiently regenerate the heart after a heart attack

A study by scientists from the University of California at Davis Health showed that blocking the inflammation-related enzyme sEH allows stem cells to repair damaged heart tissue.

Soluble epoxidehydrolase (sEH), a factor that plays a major role in triggering the activation of inflammatory processes and leading to the development of chronic inflammation in diseases of the lungs and joints. The enzyme has now become the focus of heart disease researchers.

The authors hope that their work will lead to the development of a powerful new class of compounds that can prevent cell death and muscle thickening associated with heart failure. These complications are usually associated with cardiovascular disease or heart attack.

The results of a study conducted in mice led by cardiologist Nipavan Chiamvimonvat are published in Stem Cells Translational Medicine.

“The science of using stem cell treatments for heart disease has been full of promise but little progress”, – Chiamvimonvat said. “The inflammation that accompanies heart disease is simply not conducive to stem cell survival.”

Previous studies have shown that stem cells transplanted into the heart are significantly depleted in a very short period of time.

“We think we’ve found a way to quiet that inflammatory environment, giving stem cells a chance to survive and do the healing work we know they can do”, – said lead author and cardiovascular medicine researcher Padmini Sirish. 

Dangerous disease

The occurrence of heart failure is associated with a malfunction of the heart, as a result of which the efficiency of blood circulation decreases and, as a result, the delivery of oxygen to all parts of the body worsens. Patient survival five years after diagnosis is about 45-60%. In the United States, this disease affects approximately 5.7 million people, and the annual cost is almost $ 30 billion. By 2030, it could affect up to 9 million people, and treatment will require nearly $ 80 billion.

Chiamvimonvat’s clinical practice often includes patients with heart failure and it is difficult for her to come to terms with the lack of effective medications, especially for advanced disease in the later stages.

Today, the best methods of treating end-stage heart failure are considered to be surgery – heart transplant or mechanical heart pump.

Chiamvimonvat hopes her findings will help create a two-step treatment for end-stage heart failure that combines an sEH-blocking drug with stem cell transplantation.

Testing new therapy

Chiamvimonvat and her team conducted the practical part of the study in mice using cardiomyocytes that were derived from human induced pluripotent stem cells (iPSCs). IPSCs are cells taken from adult tissue (usually skin or blood) and genetically modified to reverse their development and cause them to function as embryonic stem cells with the ability to form all types of cells.

The team used a specific sEH enzyme inhibitor, TPPU. This choice was based on the work of one of the co-authors of this study, oncologist Bruce Hammock. His lab has provided detailed studies of nearly a dozen enzyme inhibitors.

The researchers studied six groups of mice with induced heart attacks. The group that received treatment with a combination of an inhibitor and human iPSCs showed the best results in engraftment and survival of transplanted stem cells. This group also had reduced scarring of the heart muscle and improved heart function.

“Taken together, our data suggests that conditioning iPSC cardiomyocytes with sEH inhibitors may help the cells to better survive the harsh conditions in the muscle damaged by a heart attack”, – Hammock said.

The last steps before clinical trials

Chiamvimonvat and her team intend to test this approach in a research model of larger animals to better understand the beneficial role of TPPU. Scientists are also going to test the effectiveness of the method in the treatment of other heart conditions, including atrial fibrillation. Their ultimate goal is to launch human clinical trials to test the safety of treatments.