Stem Cells in the Heart

So why can’t the heart repair itself like other tissues? Some tissues, like skin and blood, are renewed by adult stem cell populations that live within those tissues, dividing to replace cells lost to wear and injury. For example, the lining of the gut replaces itself within days using stem cells.  

The heart doesn’t have an equivalent reserve of stem cells. Heart muscle cells, or cardiomyocytes, are mostly made before birth and shortly after. Once you’re an adult, almost all of your cardiomyocytes are the same cells you’ll have for the rest of your life. So when the heart is damaged, for example by a heart attack, scar tissue is formed in that area instead of new muscle. Scar tissue can patch the damage, but it doesn’t contract and pump blood in the same way muscle does, which is why heart attack damage tends to be permanent and can lead to long-term problems like heart failure.  

It was previously thought that there were cardiac stem cells (CSCs) living in the adult heart that could form new cardiomyocytes. Some researchers reported finding cells that could do this, both in lab experiments and in living animal models. But when other scientists tried to repeat these experiments, they couldn't get the same results, so this idea has mostly been abandoned. It has now been shown that the adult heart does not contain its own stem cells. The only heart-related stem cells that are known to exist are found in embryos during early development, or appear briefly when iPSCs or embryonic stem cells are being turned into heart cells in the lab. 

Currently there are no proven stem cell treatments for any type of heart disease, although some patients have had human ESC- or iPSC-derived cardiomyocytes transplanted in their hearts. 

Early Research

Earlier clinical trials generally focused on using several types of cells, some of which are listed below. These various cell types come from different sources, either from donors or the patients themselves. They have different properties, and don't all behave the same way after transplantation. 

• Haematopoietic stem cells (HSCs) are the cells responsible for generating all new blood cells (both red and white cells).   
• Cardiac stem cells (CSCs) were once thought to be stem cells found in the adult heart that could form cardiomyocytes. It has now been shown that the heart does not contain it's own stem cells. The only cardiac progenitors known are either present in the embryo during development, or are found in intermediate stages of differentiation of iPSCs or ESCs.  
• MSCs are another type of cell that have been used in cell therapies, but their identity is somewhat controversial. Generally, MSCs have been reported to make bone, fat (adipose) and cartilage tissues in the laboratory. MSCs have been isolated from fat, bone marrow, umbilical cord blood, and muscle. However, there is ongoing debate among researchers if the MSCs obtained from these different tissues are really the same. Again, there is no consensus on the precise identity of MSCs.  
• Bone marrow-derived mononuclear cells (BMMCs) are a mixture of cell types taken from bone marrow. These can include white blood cells, progenitor cells that form blood cells or bone/cartilage, MSCs and HSCs. The vast majority of cells in a BMMC sample will be white blood cells (immune cells) and progenitor cells that do not have stem cell properties.

Since the year 2000, doctors and scientists have run many clinical trials see if cell therapy for damaged hearts is safe and effective. The results have been mixed. It can be difficult, even for researchers, to understand the results that are seen in trials, especially if a trial is only conducted with a small number of people. Many of the earliest trials looked promising, but they used small patients, or older, less accurate ways of measuring results. When scientists ran bigger, better trials afterwards, most found that the treatment showed only a small improvement. Overall, even the best results so far haven’t beaten what regular heart medicine can already do.  

Scientists now know that cells from bone marrow (or other body tissues) can’t actually turn into heart muscle cells once they’re placed in the heart. What actually happens is that some of these cells merge with existing heart cells, which makes it look like they transformed, even though they didn’t. Even so, clinical studies using bone marrow cells (BMMCs and HSCs) have continued, because scientists hoped these cells might help the heart in some other way.  

Although these trials haven’t found a treatment that really works yet, they have shown that several of these treatments are at least safe.  They’ve also helped scientists figure out why the treatments aren’t working well. The biggest problem is that cells used for the treatment don’t stay in the damaged part of the heart, mostly because they don’t survive long or properly connect with the heart tissue around them.  They also don’t turn into working cardiomyocytes, which is what a damaged heart actually needs.

There are still several clinical trials currently using stem cells of different kinds to treat heart disease. But just because a treatment is offered through a ‘listed’ clinical trial does not mean that treatment will work or that it is risk-free. Many listed clinical trials are still using bone marrow stem cells and methods that have not been proven to work. There have even been cases where people have been hurt by unproven stem cell treatments. A lot remains unknown about whether these treatments truly help, or what happens to patients in the long run.  

Unfortunately, this field of research has had a large number of published results retracted from the scientific literature because the data was manipulated to support positive conclusions and outcomes or was incorrectly reported. None of the stem cells used in those retracted trials had actually become real heart muscle cells. Scientists now know that only two types, embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) are capable of that. Because there are so many different kinds of stem cells involved, it’s hard for patients, and even doctors, to fully understand what’s actually being offered.  

Most scientists agree that more lab research is still needed before a heart treatment can be made both safe and truly effective. 

Basic research: Many researchers are focused on studying the heart and stem cells. Some of this work is considered ‘fundamental’ or ‘basic’ research, which means it will help us learn about how the heart works, but might not result in a new therapy. However, this research is important to create the knowledge needed to come up with new treatments.  

Therapeutic research: Making new treatments for heart disease and damage begins with studies on cells and animals to test whether the treatment is safe and works properly. Lots of laboratory evidence must be collected before a clinical trial may be conducted on people. Clinical trials then test whether a new treatment is safe, effective and better than what is already available. 

There are many clinical trials in progress to examine stem cell treatment of the heart. A comprehensive list of studies investigating stem cells to treat the heart can be found at clinicaltrials.gov. Please note that this public website only lists clinical trials. It does not check if the listed clinical trials are safe, scientifically sound or carried out by reputable institutions.

Embryonic stem cells and induced pluripotent stem cells (iPS cells) can both be grown in a lab to make two useful types of cell: cardiac stem cells (CSCs) and cardiac muscle cells (cardiomyocytes) in laboratories. Scientists have come up with several different ways to make cardiomyocytes, and they keep studying and adjusting these methods to produce better-quality cells. There have been several exciting advances in this area.  

One team found that using three specific components helped them make make high-quality cardiomyocytes from human iPS cells. Several groups have developed systems to grow much bigger batches of cardiomyocytes at once. This is important, because treating just one heart attack patient will likely need around one billion cells. Other researchers have been working on CSCs instead. Their idea is that once these cells are placed in the heart, they could grow into all the different cell types needed to repair it, not just cardiomyocytes. 

Researchers are also using cardiomyocytes grown in the lab to test or identify new drugs that could help the heart. 

These are exciting steps forward, but there’s still a lot of work left to do. Researchers have noticed that the cardiomyocytes grown in labs don’t yet fully mature into functioning heart muscle, although recent research has shown ways to fix this. Learning how to grow cells that are fully functional will be key to making these treatments actually work.  

Several other challenges are also being addressed. For example, any transplanted heart cells that beat would need to beat in time with the rest of the heart. Another problem is getting lab-made cells to properly connect with the surrounding tissue and survive in the damaged parts of the heart. Most studies show only a small number of cells survive after cell transplants, but some researchers have found new methods to help cells form bigger, healthier patches of heart muscle in the lab. One difficulty transplanting stem cells into the heart is that the cells do not stay near the damaged tissue, but flow with the blood out of the heart into vessels of the lung. New ways are being investigated to address this. For example, researchers have found a way to grow a ‘heart patch’ containing cardiomyocytes grown from stem cells. The patch is implanted onto the wall of the outside of the damaged heart, strengthening it and improving its function. This allows many more heart muscle cells to be transplanted, and helps them stay in place and survive. This is currently being tested in a clinical trial. 

Finally, scientists need to make sure only the right cells get used in the treatment. Both embryonic stem cells and iPS cells are pluripotent, meaning they’re able to turn into almost any cell type in the body. This is what makes them powerful as a potential therapy, but it also carries a risk. If these cells aren’t carefully controlled, they can grow into cancerous tumours instead. That’s why it’s so important to separate the pluripotent stem cells from CSCs and cardiomyocytes before any cells are used for transplantation. 

We can now grow cardiomyocytes in the lab, but the future still holds many questions and hopes. How will we make sure that transplanted cells correctly connect and survive in only the damaged heart? Can we make the transplanted cells work together with heart muscle still there? One day, will we be able to stimulate the heart to regenerate itself without transplanting cells?  More research is needed to answer these questions, and to continue developing new treatments. 

By better understanding the normal development and function of the heart we may learn how to promote the heart to heal itself. Researchers also are studying the natural repair and regeneration of the heart in other animals. Zebrafish have a remarkable ability to regenerate their hearts if they are damaged. The hearts of newborn mice can regenerate, but mice lose this ability as they mature. Understanding regeneration in other animals may reveal how to make better cardiomyocytes for transplantation, or how to turn on natural repair mechanisms in the human heart. 

Interview with Christine Mummery: A physicist's take on stem cell biology

Fact sheet on Regeneration: what does it mean and how does it work?

Are Lab-Grown Hearts the Key to Long Life? | Secrets of the Human Body | BBC Earth Science

World Health Organization (WHO) page on cardiovascular diseases

This factsheet was created by Stefan Jovinge, coordinator or the EC funded project CardioCell.

Reviewed in 2015 by Christine Mummery.

Edited and updated in 2018 by Ryan Lewis.

Reviewed in 2019 by Christine Mummery.

Reviewed in 2025 by Christine Mummery, Wolframm Zimmerman and Olaf Bergmann. 

Cell images by Stefan Jovinge. Lead image of human heart by Gordon Museum/Wellcome Images.