Although stem cells have been around for a long time and research is ongoing, new knowledge raises even more questions that researchers are trying to answer.
“The challenge for stem cell biologists and biochemists is to understand how humans can control cells and their functions. Once we know this, I think it will be possible to apply stem cells on a large scale,” says Dr. Daiva Baltriukienė, a biochemist at Vilnius University Life Sciences Center.
According to the researcher, while the potential is great, each new development raises new questions and uncertainties. Therefore, therapeutic options offered by biobanks and clinics abroad should be viewed critically for the time being. Our discussion covers stem cells, tissue and organ engineering, neuroinflammation, and neurodegenerative diseases.
Q: In your opinion, what are the most promising developments in the therapeutic use of stem cells?
A: In my opinion, stem cells will become a therapeutic tool in the future, that will be useful in the treatment of various diseases. But it may take a long time before that happens. Embryonic stem cells were discovered 63 years ago, but as far as I have looked at the clinical trials, they are mainly used for the treatment of leukemia. In addition, the cell products are most often used, not the cells themselves.
Although many serious studies have been carried out in vitro (in test tubes) and have shown how the functions of stem cells can be regulated, this does not reflect 100% of the processes in a living organism.
Our body is a complex entity, and various factors influence the cells that make it up. Even if we learn to predict and control the response and fate of cells in the test tube, the outcome in the body may be completely different. And our organisms differ: over the years, we are exposed to various external influences, both at the micro and macro levels, and inflammations develop.
I looked at the latest data on how food affects intestinal stem cells. It turns out that the number of stem cells in the gut depends on diet, as the epithelial layer of the gut needs to renew itself. The gut is shaped so that there is a niche for stem cells, from which new differentiated cells are formed. So, food does affect the number of stem cells, and the number affects what kind of cells the stem cells turn into.
Q: What do you mean when you say ‘what kind of cells’?
A: Stem cells are not specialized; they can specialize into various cells with different functions. All the tissues and organs in the human body are not made up of one type of cell but from several to dozens of different cell types. The gut is no exception. Certain signals are given to the cells that seem to tell them to differentiate into a particular cell, which is necessary for one specific function in the body.
Q: And if we eat stem cell-friendly food, what are the most significant benefits for our bodies?
A: It's not just gut health that depends on what we eat. It's where many bacteria live, digesting food, forming metabolites that enter the bloodstream, and traveling to different tissues, organs, and even the brain. Therefore, food has an impact on our well-being. You may have noticed that we feel differently when we eat certain foods: some make us sleepy and wanting to lie down, others make us feel energetic and wanting to do something.
The more stem cells you have, the greater the regenerative potential of your gut. And this applies not only to the gut but also to other organs and tissues. In recent years, a wide variety of stem cells have been identified in the body, mostly called mesenchymal stem cells. Tissues are made up of different cells adapted to perform a specific function, such as secretory in the liver and contractile in the heart. Stem cells can become any cell, allowing them to proliferate, migrate to where they need to go, etc. For example, stem cells travel via circulation to an organ that has been damaged to replace those dead tissue cells. The regenerative potential is, therefore, very important - the tissue can maintain its pre-inflammatory functions or heal by forming a scar.
Q: Do I understand correctly that we do not yet know most of the factors related to the amount of stem cells in our body?
A: The task of stem cell biologists and biochemists is to understand how human beings can control cells and their functions. Once we know this, I think that stem cells will be able to be used on a large scale. We know a lot now, but that knowledge raises even more questions.
Stem cell research peaked in the 21st century, and in 2004, we started research in Lithuania. The aim then was to use these cells to regenerate the heart after a heart attack. At that time, it was not known that there were stem cells in the heart, but now it is known. Only the quantity is rather small to repair major heart damage. Then came the idea of taking cells from the skeletal muscle and transferring them to the heart. A lot of clinical trials were carried out. However, it turned out that it is not all that simple; there are many side effects, and the population of stem cells in other muscles is not identical to the stem cells in the heart. I was looking at what has changed in this area over the years. There are studies, even some that have reached the clinical stage, but the problems are the same. Not much has moved forward.
Similarly, with tissue engineering. More than ten years ago, it was thought that researchers would quickly learn how to construct complex artificial tissues, but today, while intensive research continues, things have settled down. We have not yet seen a significant breakthrough.
Q: In Lithuania, there is a service that harvests stem cells from the umbilical cord of a newborn baby and stores them in case they are ever needed to treat leukemia and other diseases. How reliable is this process, considering there is still so much we do not know? Could it be that science is being forestalled?
A: Indeed, there is such a service in Lithuania. In the past, it was pretty popular. There were several biobanks, some of which are still in operation today. However, researchers have started to ask questions, such as whether long-term storage of cells changes their properties. We don't have long-term data on whether a cell changes genetically and epigenetically. I do not doubt that if we were to carry out extensive research, we would certainly find that stored cells do change. And who knows how they will work in the body when the person whose umbilical cord cells have been taken develops a disease as an adult decades later. But since most of these children are now only teenagers, maybe by the time they need the cells, for example, when they reach a respectable age, science will have advanced to the point where it will be able to take control of the cells, to return them to their original state.
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Q: You’ve mentioned tissue engineering. What does the process look like when growing tissue?
A: It takes a very large group of people with different backgrounds to develop a tissue because the principles of tissue engineering have only recently been developed. Three main things have been identified as being needed: stem cells, the extracellular environment, and factors that regulate the cells. Cells and the factors that regulate cells are part of our group's research. It takes engineers, physicists, chemists, and medics to create the proper extracellular environment because they are the ones who have to confirm that the tissue engineered is functioning as it should so that it can be used to replace the damaged tissue.
Q: One of the most remarkable examples of tissue engineering occurred in 1996 when an ear was grown on a laboratory mouse.
A: This experiment was carried out at the early dawn of tissue engineering. However, in this case, the ear is not grown but created from a polymeric material that is used as a scaffolding for the cells to keep their shape. The experiment showed that the scaffolding could be shaped to the desired form and that the material was biocompatible - which means that when implanted under the skin of a mouse, an ear-like structure was formed.
For example, now that 3D printing has become so popular, researchers have proposed using it to create tissue. Research has started on a particular group of polymers – hydrogels – that are perfectly biocompatible with cells. Many different techniques have already been developed.
But a lot of it is... how should I put it better... perhaps like children playing, doing something, having fun, so do researchers: we do it, we are glad, it's fun, we've made a step forward, but what's next? And beyond that, there are lots of unanswered questions.
Q: What is the most difficult tissue to produce from the human body? Is it brain tissue, for example?
A: Brain tissue is challenging to produce, even impossible. I have read that it is impossible to define clearly how hard or soft the brain is. After all, you cannot measure it in a healthy person because it requires intervention. Intervention is when something is wrong, and when there is something wrong, the question is whether it has affected the extracellular environment.
Other tissues and organs vary in complexity according to how unique and specialized a function they are adapted to perform and how many different cell types they are made up of. These include secretory tissues such as the liver and kidneys.
The most remarkable progress has been made in our largest organ, the skin. It is a relatively simple organ that is most often damaged. Cartilage and bone tissue come second. The cartilage tissue is probably because it has very few cells and is composed mainly of the extracellular environment.
Q: Does artificial tissue or organ age?
A: I think so; everything happens in it, just like it happens in the body. However, there have not been many artificial tissue transplants yet, only isolated cases in critical conditions. Cells in a test tube age, so there is no reason to believe it is different in the body.
Q: The last topic I would like to discuss from your research interests is neuroinflammation. What role does neuroinflammation play in neurological disorders?
A: Neuroinflammation is usually the beginning of all neurodegenerative diseases. This is why we are trying to identify the ‘leading players’ in neuroinflammation.
So far, we are only studying one type of cell: microglia cells. These are brain macrophages that live naturally in the brain and function during neural tissue development. Well, and very interestingly, these cells can be in two states: when they protect against inflammation and act anti-inflammatorily, and when they promote inflammation.
We work with animal cells. Our group's task is to find out how these cells are regulated in different contexts. The initial idea was to see if they are influenced by diet. For example, we induce diabetes in mice because we want to know whether all the processes involved lead to neurodegenerative diseases such as Parkinson's disease. In other words, we aim to check whether a human diet is linked to the onset of neuroinflammation. Dietary habits can both regulate and initiate the inflammatory process.
We want to detect the very onset of neurodegenerative diseases when there are no clinical symptoms so that we can find ways to prevent the development of such conditions in the future.
Q: Thank you for talking to me.
A: Thank you.
Interviewed by Goda Raibytė-Aleksa
Photo credits: VU LSC archives.