Heart Disease – Closer Look at Stem Cells

Posted: June 9, 2017 at 10:43 am

Cardiovascular disease is the number one cause of death worldwide in men, women and children, claiming more than 17 million lives each year. The effects of congestive heart failure and acute myocardial infarction (heart attack) present great challenges for doctors and researchers alike.

In this section:

Heart attacks cause damage to the heart muscle, making it less efficient at pumping blood throughout the circulatory system.

Your heart is constructed of several types of cells. For mending damaged heart tissue, researchers generally focus on three specific heart cell types:

Gladstone Institutes. Close up of a mouse heart stained to reveal the important structural protein that helps heart muscle cells to contract (red). The cell nuclei are labeled in magenta.

Despite major advances in how heart disease is managed, heart disease is progressive. Once heart cells are damaged, they cannot be replaced efficiently, at least not as we understand the heart today.

There is evidence that the heart has some repair capability, but that ability is limited and not yet well understood.

Heart failure is a general term to describe a condition in which the hearts blood-pumping action is weaker than normal. How much weaker varies widely from person to person, but the weakness typically gets worse over time. Blood circulates more slowly, pressure in the heart increases, and the heart is unable to pump enough oxygen and other nutrients to the rest of the body. To compensate, the chambers of the heart may stretch to hold more blood, or the walls of the chambers may thicken and become stiff. Eventually, the kidneys respond to the weaker blood-pumping action by retaining more water and salt, and fluid can build up in the arms, legs, ankles, feet, and even around the lungs. This general clinical picture is called congestive heart failure.

Many conditions can lead to congestive heart failure. Among the most common are:

The American Heart Association defines normal blood pressure for an adult as 120/80 or lower. What do those numbers mean? The top number is the systolic pressure that is, the pressure in your arteries when your heart beats, or contracts. The bottom number measures diastolic pressure, or the pressure in your arteries between beats, when the heart refills with blood.

In the early stages of congestive heart failure, treatment focuses on lifestyle changes (healthy diet, regular exercise, quitting smoking, etc.) and specific medications; the goals are to slow down any progression of the disease, lessen symptoms and improve quality of life.

Medications called beta blockers are often prescribed after a heart attack or to treat high blood pressure. Other medications called ACE inhibitors prevent heart failure from progressing.

For moderate to severe congestive heart failure, surgery may be necessary to repair or replace heart valves or to bypass coronary arteries with grafts. In severe cases, patients may be put on fluid and salt restriction and/or have pacemakers or defibrillators implanted to control heart rhythms.

Acute myocardial infarction, or a heart attack, occurs when the blood vessels that feed the heart are blocked, often by a blood clot that forms on top of the blockage. The blockage is a build-up of plaque that is composed of fat, cholesterol, calcium and other elements found in the blood. Without oxygen and other nutrients from the blood, heart cells die, and large swaths of heart tissue are damaged.

After a heart attack, scar tissue often forms over the damaged part of the heart muscle, and this scar tissue impairs the hearts ability to keep beating normally and pumping blood efficiently. The heart ends up working harder, which weakens the remaining healthy sections of the heart; over time, the patient experiences more heart-related health issues.

Doctors often use a procedure called angioplasty to disrupt the blood clot and widen clogged arteries. Angioplasty involves inserting and inflating a tiny balloon into the affected artery. Sometimes this temporary measure is enough to restore blood flow. However, angioplasty is often combined with the insertion of a small wire mesh tube called a stent, which helps keep the artery open and reduces the chances that it will get blocked again.

Other post-heart attack treatments include the regular use of blood thinners (for example, low-dose aspirin) to prevent new clots from forming and other medications to help control blood pressure and blood cholesterol levels. Lifestyle changes, such as lowering salt and fat intake, exercising regularly, reducing alcohol consumption and quitting smoking are also recommended to reduce the chances of a subsequent heart attack.

Scientists and clinicians have long suspected and recently confirmed that a persons genetic makeup contributes to the likelihood of their having a heart attack. Learn more here

The goals of heart disease research are to understand in greater detail what happens in heart disease and why, and to find ways to prevent damage or to repair or replace damaged heart tissue. Scientists have learned much about how the heart works and the roles different cells play in both normal function and in disease, and they are learning more about how cardiomyocytes and cardiac pacemaker cells operate, including how they communicate with each other and how they behave when damage occurs.

Researchers grow cardiomyocytes in the lab from the following sources:

These cells will beat in unison in a culture dish, the same way they do in a living heart muscle. This is exciting to consider, as researchers explore whether they might someday grow replacement tissue for transplantation into patients. However, it is not yet known whether lab-grown cardiomyocytes will integrate or beat in unison with surrounding cells if they are transplanted into the human body.

Gordon Keller Lab. Heart cells beating in a culture dish.

Scientists also use various types of stem cells to study the hearts natural repair mechanisms and test ways to enhance those repair functions. The evidence we have so far suggest thats the heart may have a limited number of cardiac stem cells that may conduct some repair and replacement functions throughout an individuals life, but we dont know where they live in the heart or how they become activated.

Human cells made from iPS cells are also incredibly useful for creating human models of heart disease to get a better understanding of exactly what goes wrong and for testing different drugs or other treatments. They can also be used to help predict which patients might have toxic cardiac side effects from drugs for other diseases such as cancer.

The key to treating heart disease is finding a way to undo the damage to the heart. Researchers are trying several tactics with stem cells to repair or replace the damaged heart tissue caused by congestive heart failure and heart attacks.

Areas under investigation include:

The Europe-wide BAMI clinical trial (the effect of intracoronary reinfusion of bone marrow-derived mononuclear cells on all-cause mortality in acute myocardial infarction) that began in 2014, is testing the infusion of cells from the participants bone marrow into one of the coronary arteries (one of two major arteries that supply the heart) to spark repair activity. However, it is not yet clear whether these cells will support heart repair function or in what way.

Researchers are also exploring transplantation of cardiomyocytes generated from both iPS cells and cardiac progenitor cells. They need to determine whether these transplanted cells survive and function in the body and whether they help speed up the hearts innate repair mechanisms.

Some of these approaches are still being evaluated in the lab while others are already being tested in clinical trials around the world. However, these trials are in their early stages and the results will not be clear for many years. Indeed, some published data conflict in critical ways, so carefully designed and well-monitored trials are key to working out what is safe and effective.

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Heart Disease - Closer Look at Stem Cells

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