Replacing Dead Cardiac Tissue After a Heart Attack: Two Discoveries
Exciting and Potentially Important Discoveries
When someone experiences a heart attack, cells in their heart die. Unlike the case in some parts of the body, the dead cells aren’t replaced with new ones. This means that not all of the patient’s heart beats after their recovery, despite medical treatment for the heart attack. The patient may experience problems if a large area of their heart is damaged.
Two groups of scientists have created potential solutions for the problem of dead cardiac tissue. The solutions work in rodents and may one day work in us. One solution involves a patch containing heart cells derived from stem cells. The patch is placed over the damaged section of the heart. The other involves the injection of a gel containing microRNA molecules. These molecules indirectly stimulate the replication of heart cells.
Most heart attacks occur when a coronary artery in the heart becomes blocked. Doctors can often (but not always) treat the symptoms of a heart attack, prevent further damage to the heart, and help the body deal with the results. At the moment, they can’t replace dead heart cells to any significant extent, however.
Heart Cells and Their Function
The heart is a hollow sac with muscular walls. The walls consists of specialized muscle cells found nowhere else in the body. Most of these cells contract when electrically stimulated. (In the body, the electrical current in nerves and muscles is created by the flow of ions, not electrons.) Heart cells are also known as cardiac muscle cells, cardiocytes, cardiac myocytes, and myocardiocytes.
There are two types of heart cells: contractile cells, which produce the heartbeat as they contract in unison, and pacemaker cells, which stimulate the contractile cells. The contractile cells far outnumber the pacemaker ones. Pacemaker cells are very important, however. They are found in the sinoatrial or SA node, which is also referred to as the pacemaker of the heart. The node is located in the wall of the upper part of the right atrium, as shown in the illustration below. It creates the electrical impulses, or action potentials, that stimulate the contraction of the heart. The SA node is in turn stimulated by the autonomic nervous system of the body.
An artificial pacemaker can be implanted in the heart to help SA node and electrical conduction problems. When contractile cells die, however, they can't be replaced. They no longer respond to electrical stimulation and don’t contract. Scar tissue often forms in the area. A large area of damaged heart tissue may be debilitating for the patient and may lead to heart failure. The term "heart failure" doesn't mean that the heart stops beating, but it does mean that it can't pump blood well enough to provide all of the body's needs. Everyday activities may become difficult for the patient.
The electrical conduction system of the heart is made of specialized muscle cells. It's shown in blue in the diagram below. Structure 1 is the SA node.
Duke University scientists have created a patch that could be placed over the damaged area of a heart and trigger tissue regeneration. The patch contains specialized cells derived from stem cells. Stem cells are unspecialized but have the ability to produced specialized cells when stimulated correctly.
Stem cells are a normal component of our body, but except in specific areas they aren't abundant and aren't active. The activated cells offer the exciting possibility of replacing body tissues and structures that have been damaged or destroyed.
Stem cells have different potencies. The word "potency" refers to the number of cell types that a stem cell can produce.
- Totipotent stem cells can produce all of the cell types in the body as well as the cells of the placenta. Only the cells of the very early stage embryo are totipotent.
- Pluripotent cells can produce all of the cell types in the body. Embryonic stem cells (except for those of the very early stage of development) are pluripotent.
- Multipotent cells can produce only a few types of stem cells. Adult (or somatic) stem cells are multipotent. Though they're referred to as "adult" cells, they're found in children, too.
In an interesting advance in science, researchers have discovered how to trigger specialized cells from our bodies to become pluripotent. These cells are known as induced pluripotent stem cells to distinguish them from the natural ones in embryos.
Early Symptoms of a Heart Attack
It's vital that anyone who may be experiencing a heart attack gets to a doctor as soon as possible in order to reduce the damage to the heart muscle.
A Patch for a Damaged Heart
According to the Duke University news release referenced below, stem cells likely to produce heart muscle cells have been injected into ailing human hearts in clinical trials. The release says that "there do seem to be some positive effects" from the procedure, but most of the injected stem cells have either died or have failed to produce cardiac cells. This observation suggests that a improved solution to the problem is needed. The Duke scientists think that they may have found one.
The scientists have created a patch that is likely large enough to cover damage in the human heart. The patch contains a variety of heart cells derived from pluripotent stem cells. Both natural stem cells from embryos and induced ones from adults produce the required cells. The cells are placed in a gel in a specific ratio. Researchers have discovered that humans cells have the amazing ability to self-organize when placed in a suitable environment, as happens in the gel patch. The patch is electrically conductive and able to beat like heart tissue.
The patch isn't ready for human use yet. Improvements need to be made, such as increasing the thickness of the patch. In addition, a way of fully integrating it into the heart needs to be found. Smaller versions of the patch have been attached to mouse and rat hearts and have functioned like heart tissue, however.
A Beating Heart Patch (No Sound)
In order to understand the details of the second experiment related to heart repair, it's helpful to know a little about two nucleic acids—DNA and messenger RNA. A DNA molecule has the shape of a double helix. In the illustration below, part of the molecule has been flattened in order to show its structure more clearly.
DNA: A Basic Introduction
DNA, or deoxyribonucleic acid, is present in the nucleus of almost every cell of our body. (Mature red blood cells don't contain a nucleus or DNA.) A molecule of DNA consists of two long strands twisted around each other to form a double helix. Each strand consists of a sequence of "building blocks" known as nucleotides. A nucleotide consists of a phosphate, a sugar called deoxyribose, and a nitrogenous base (or simply a base). There are four bases in DNA: adenine, thymine, cytosine, and guanine. The molecular structure can be seen in the illustration above.
The bases of a single DNA strand repeat in different orders, like the letters of the alphabet as they form words in sentences. The order of the bases on a strand is very significant because it makes up the genetic code that controls our body. The code works by "instructing" the body to make specific proteins. Each segment of a DNA strand that codes for a protein is referred to as a gene. A strand contains many genes. It also contains sequences of bases that don't code for proteins, however.
The bases on one strand of the DNA molecule determine the identity of those on the other strand. As the illustration above shows, adenine on one strand always joins with thymine on the other, while cytosine on one strand joins with guanine on the other.
Only one strand of a DNA molecule codes for proteins. The reason why the molecule must be double stranded is beyond the scope of this article. It's an interesting question to investigate, though.
In the artistic representation of the DNA molecule shown above, the sides of the "ladder" represent the phosphate-deoxyribose backbone of each strand and the rungs represent the bonds between the bases that hold the strands together.
Genes control the production of proteins. DNA is unable to leave the nucleus of a cell. Proteins are made outside the nucleus, however. One type of RNA (ribonucleic acid) solves this problem by copying the code for making a protein and transporting it to where it's needed. The molecule is known as messenger RNA or mRNA. An RNA molecule is quite similar to a DNA one, but it's single-stranded, contains ribose instead of deoxyribose, and contains uracil instead of thymine. Uracil and thymine are very similar to each other and behave the same way with respect to binding to other bases.
The two strands of a DNA molecule temporarily separate in the region where RNA is being made. The individual RNA nucleotides come into position and bind to those on one strand of the DNA (the template strand) in the correct sequence. The sequence of bases in the DNA strand determines the sequence of bases in the RNA. The RNA nucleotides join together to make the messenger RNA molecule. The process of making the molecule from the DNA code is known as transcription.
Once its construction has finished, the messenger RNA leaves the nucleus through pores in the nuclear membrane and travels to cell organelles called ribosomes. Here the correct protein is made based on the code in the RNA molecule. The process is known as translation. Nucleic acids are made of a chain of nucleotides while proteins are made of a chain of amino acids. For this reason, making a protein from the RNA code could be viewed as translating from one language to another.
More Details About Transcription
There are other types of RNA in our cells besides messenger RNA. One of these types is microRNA, or miRNA. This is the kind that may be significant in healing the heart. All kinds of ribonucleic acid in our body are made by transcription from DNA, as described above. They have different functions from one another, however.
The second potentially important discovery with respect to heart muscle regeneration comes from scientists at the University of Pennsylvania. It relies on the action of microRNA molecules, which are short strands containing non-coding bases. Each molecule contains about twenty bases. The molecules belong to a group known as regulatory RNA.
Regulatory RNA molecules are not as well understood as the RNA molecules involved in protein synthesis. They seem to have many important functions and are thought to play a role in a wide variety of processes, however. Many scientists are exploring their actions. MicroRNA is a relatively recent and very interesting discovery.
Gene expression is the process in which a gene becomes active and triggers the production of a protein. MicroRNA is known to interfere with a protein's manufacture, often by inhibiting the action of messenger RNA in some way. By doing this, it's said to "silence" the gene.
Facts About MicroRNA From a Harvard Professor
An Injectable Gel for the Heart
The reasons why heart cells don't regenerate isn't completely understood. In the hope of repairing damage to mouse hearts, University of Pennsylvania scientists created a mix of miRNA molecules known to be involved in cell replication signaling. They placed the molecules in a hyaluronic acid hydrogel and then injected the gel into the hearts of living mice. As a result, the scientists were able to inhibit some of the "stop" signals that prevent heart cells from reproducing. This allowed new heart cells to be generated.
Signaling pathways often involve specific proteins. The miRNA molecules may have worked by inhibiting the formation of these proteins via their interference with messenger RNA molecules.
As a result of the treatment with miRNA, the mice who had experienced a heart attack "showed improved recovery in key clinically relevant categories". These categories reflected the amount of blood pumped by the heart. In addition to showing functional improvements in the mouse hearts after treatment, the researchers were able to demonstrate that the cardiac muscle cells had increased in number.
The researchers are aware that using miRNA to inhibit "stop" signals and indirectly promote cell replication could be dangerous instead of helpful. Increased cell division occurs in cancer. A problem could also develop if the miRNA molecules trigger reproduction of cells other than contractile cells in the heart. The scientists want to promote the proliferation of heart cells for long enough to be helpful and then to stop the process. This is one of the goals of their future research.
The next goal of the University of Pennsylvania scientists is to experiment with human cells in lab equipment. They then plan to explore the effects of the gel in animals whose heart is more similar to that of humans, such as pigs.
Hope for the Future
Although the new techniques described in this article have only been used on rodents at the moment, they offer hope for the future. The two news reports that I describe were released on successive days, even though the studies were performed by scientists from different institutions. This might be a coincidence, or it might indicate that the amount of research into helping damaged hearts recover is increasing. This could be good news for people who need help.
References and Resources
- A list of common symptoms of a heart attack from the Mayo Clinic
- Treatments for a heart attack from the NHLBI or National Heart, Lung, and Blood Institute (Like the above website, this site has other helpful information about heart attacks.)
- Stem cell information from the National Institutes of Health
- DNA and RNA information from the Khan Academy
- Information about a beating heart patch from Duke University
- Facts about an injectable gel that helps heart muscle to regenerate from the Medical Xpress news site
© 2017 Linda Crampton