He studied biochemistry and then immersed himself in the research world.

The truth is, at first I wanted to be a marine biologist. But as my career progressed, I fell in love with cellular and molecular biology. As we said throughout the career, I went from being a biologist with boots to a biologist with a apron. In the practices performed in the Bachelor of Biochemistry I realized that I liked the research, I have always wanted to know new things and know what better than trying to understand what I don't know.

The passion for knowing how life works at the molecular and cellular levels started with my teachers. Moreover, I was fascinated to see with what accuracy are organized the processes that occur at the smallest levels of life. In the same vein, knowing the special characteristics and applicability of stem cells allows us to turn them into a health tool while learning more about them. From the very beginning I realized that it wasn't going to be an easy road, but that every day you could get to know a new thing and design new experiments is something you can't get in any other work.

In his thesis he has investigated the regeneration of damaged nerve tissues.

Although the ultimate goal was the regeneration of nerve tissues, most of the thesis focused on the neurodifferentiation capacity of stem cells from human wristbands (Human Dental Pulp Stem Cells, hDPSCs), once known the minimum of this process, to be able to use these cells in neural regeneration. Stem cells are early cells that have the ability to become any cell in the body with compromised function and morphology. In my thesis, we managed to get hDPSCs to express characteristics similar to those of neurons, using special conditions. But in addition to this, we found that these also had the ability to get the characteristics of the cells in the blood vessels. This is as important as obtaining neurons, since it is known that in many neurodegenerative diseases the integrity of blood vessels is damaged. So our goal was to first get the specialized tissue cells that we wanted to regenerate, and then integrate properly into the tissue.

The second part of the thesis tried to integrate these differentiated cells into the central nervous system, specifically into the brain. The results showed that human hDPSCs had the ability to penetrate and survive smoothly in the rat brain. In addition, they demonstrated their ability to build blood vessels and published the results in specialized scientific journals. This finding demonstrated that hDPSC have the possibility of surviving and being functional in an environment as difficult as the textile nerve.

In the same vein, we are working on possible cell therapy combining human-derived hDPSC to combat potential brain injuries and nanostructured biodegradable materials functioned with graphene. At the same time we are present the teachers and researchers of the group "Signaling Lab" of Fernando Sonda in Cell Biology and Histology of the Faculty of Medicine and Nursing to which I belong (Gaskon Ibarretxe, José Ramón Pineda and Beatriz Pardo), the group Cipolo of the School of Engineering of the UPV/EHU.

As often happens in science, opportunity came to us all of a sudden. When I arrived at Fernando Unda's team, this group was specialized in the development of teeth and structures of the mouth. A few years ago, the existence of hDPSCs was described, and Fernando and Gaskone were committed to the scientific value of these cells. At first we were immersed in the knowledge of neural characteristics and at a congress we met José Ramón Pineda. Pineda had a long and fruitful experience in neuroscience and the study of brain diseases. This was our starting point for testing the behavior of cells in nerve tissue.

They focused on some stem cells found in the pulp of the teeth.

The adaptability and differentiation ability of stem cells, tissue regeneration and the importance they can have in drug testing are a sign of this.

To answer this question, it must first be pointed out that there are different types of stem cells. Embryonic stem cells (ESCs), the early cells that we can find in the early stages of fetal development since the formation of the zygote, have the ability to become any cell in the body. They also have the ability to create a being (at least in a virtual way), but due to its origin, they bring with them some ethical headaches.

As for stem cells that we can find in the adult individual, we can distinguish two types. The first are channelled stem cells (iPSCs), to which genetic transformations have to be produced, using Yamanaka factors, so that adult cells, for example, lose their specific characteristics and become stem cells again. Although its use has no ethical implications, it can cause safety problems for the patient who has undergone therapy. It is not yet clear that the effects that genetic transformation can have on these cells in the long term (cancer formation, impaired functioning...) and on the other hand, the genetic changes and mutations that adult cells have as a result of the passage of time may arise as a result of the differentiation of these cells (uncontrollable growth, increased mutations, etc. ). ). Stem cells found in adult beings are called adult stem cells. They do not have the possibility of differentiating to any cell, as was the case with ESC, and are not as easy to obtain IPSCs, but they do not present ethical or safety problems. Adult stem cells are precursor cells found in special organs and tissues. They are remnants of cell populations that will allow the regeneration and regeneration of different organs and tissues in the path of embryonic development to the maturity of the being. We can find different populations all over the body (nerves, fat percentages, bone marrow, hematopoietic...).

We focused on the source of cells less known but easier to obtain and which will cause minimal intervention on the donor. In fact, hDPSCs are extracted from the 3 strings (the last tooth) of the biological garbage, a process that requires a small intervention compared to the liposuction and nerve tissue needed to obtain other cells.

... and you've seen that adult nerve tissue regeneration stem cells are the ones in the teeth.

Different stem cells have different benefits and capabilities, and we believe that hDPSC have strategic peculiarities for their use in future cell therapies. In fact, we say that hDPSC has an ectomesenchymal origin. That is, most facial structures (bones, teeth, muscles, nerves...) are produced by cells that detach from the ectoderm to the mesenchyme (neurons, myelinating cells Schwann...) and at the same time, the cells that form the peripheral nervous system are produced from the neural gongor (neurons).

Stem cell remnants and the phylogenetic proximity of nerve cells found in adult teeth are a strategic advantage compared to the characteristics of other stem cells to achieve nerve tissue regeneration. For example, fat stem cells or bone marrow will be much further phylogenetically removed from nerve tissue cells than from the cells we use, and hDPSC maintain the ability to transform itself into neurons or glial cells confirming the hypothesis of my thesis.

Animal sera have been used to remove and grow these cells from the teeth. But they have drawbacks ...

The removal of blood cells (erythrocytes, leukocytes...) creates a fluid called plasma. When coagulant factors are eliminated from the plasma, an element called serum is produced, composed of biological elements such as water, vitamin, proteins, hormones, glucose and growth factors. Bovine serum (FBS) is frequently used in in in vitro seeding of cells as it promotes cell growth, adhesion and survival. The use of animal serum provides advantages in the spread of crops, but also entails some disadvantages. For example, the use of non-human elements is prohibited in cell cultures to be used in human therapies, as these may excite the patient's immune system (IS). Furthermore, the composition of the serum is not fully known and it is essential to know all the elements that can affect the cells in the culture. Among other things, the serum can bring prions and viruses with it and this would be critical for the patient undergoing cell therapy. In addition, the FBS will guide the cells towards specific cell lineages. In this case it is known that the elements present in the serum can increase the differentiation towards the cells of the bone lineage in mesenchymal stem cells. In our case, we want to use hDPSC in regenerative therapies, so this spontaneous differentiation is not useful.

For cell growth, an innovative design was necessary. What have you achieved?

Although, as mentioned above, serum provides significant advantages in crop expansion, it presents significant disadvantages for cells to be used in human cell therapy. From the beginning, my job was to develop a useful protocol that did not have serum to grow at the hDPSC. We knew that the changes that would affect cells by changing growth protocols would also be important. In fact, the elimination of the FBS to the crops gave them the ability to differentiate hDPSC from other breeds.

As we have presented in recent years, we have been able to differentiate the hDPSC from neural (glia and neuron) and endothelial lineages by means of boric serum culture media. Using these special serum free media, we've managed to get hDPSC to grow in the spherical structures that we know under the name of "dentiosphere," and we've patented this. These cells are formed by the combination of the aforementioned precursor cells. By introducing them into the brains of mice, we have been able to demonstrate that they also have the ability to create new human blood vessels and integrate them into the tissues of different receptors.

What has been the finding?

The data and publications we have obtained in recent years have revealed a large amount of valuable information. Focusing on the basic knowledge of science, we have analyzed the effect of serum on the differentiation and growth capacity of hDPSCs. And as far as applied science is concerned, we have achieved the ability to modulate the hDPSC to the letter, orienting them towards the cell lines that we want to achieve in future cell therapies and making them immune sustainable.

In addition to this, we've learned that hDPSC are not only introduced, survived and integrated into the brain of a mammal, but have the ability to create human forests virtually equal to the mouse's blood forests.

What applicability can it have?

The applicability of our discoveries is unlimited. The integration of hDPSC into the brain of other animals and the creation of functional structures (blood vessels) represent an important advance in the clinical utility of these therapies. In fact, it is known that in most neurodegenerative diseases, in addition to the expected cells (glia and neurons), the cells of the neurovascular unit (endothelial, pericytes) also suffer pain. On many occasions, the guarantee of nutrients and oxygen provided by the blood can calm the symptoms of the disease and delay the pathophysiology. Consequently, in addition to the neurodifferentiation capacity of our cells, the ability to create blood vessels can be very important when dealing with neurodegenerative disease.

However, the most important benefit of our cells is their use in autologous therapies (using cells from the same patient). Among these advantages, the low invasiveness and the ease of obtaining hDPSC and the modulation capacity of IS must be taken into account. The immunomodulation capacity of hDPSCs is such that clinical trials with hDPSC have been conducted to address the cytocov-2 (COVID19) storm caused by SARS-cov-2 (IS overactivation) disease in Wuhan himself.

You defended the thesis in 2018 and are now working at the university.

Since I finished my thesis, I have had a postdoctoral DOKBERRI research fellowship and have chained several research contracts. I have continued to call for more research grants, but it is not easy to get them; there are a lot of people in the same situation and the grants are not so much. If we want to continue research in the Basque Country, competitiveness is enormous. As a society, we should reflect on the science and the importance we give to scientists, even more so after what happened with Covid19. I am clear that it will not be the only pandemic disease.

I currently work as a professor in the Physiology department of the Faculty of Medicine and Nursing at UPV/EHU. I've been working as a professor since October, and the truth is, I'm very comfortable, although it's a big challenge. To prepare classes, you have to spend a lot of time, but at the same time, it gives me the opportunity to learn new things, not only from books, but also from people. At the moment I have always had friendly groups of students, not only in the medical and nursing faculty, but also in the experience classrooms for retirees I teach in Donostia. I'm certainly learning a lot from them.

On the other hand, continuing the research is also fundamental to me and I entered the laboratory everything I can to work with hDPSC. As a result, in the laboratory of Fernando Unda, in addition to scientific quality, personal quality is also an important factor. Among those of us who form the laboratory, I'm getting a lot of support to push through the projects that we have.

He participated in the Thyothesis. What experience did you have?

It was a nice experience. We need tools to make known the research work carried out by Basque researchers, often we do not know what our attached laboratory does. It is essential to ensure collaboration in the world of science and we often move abroad to make the techniques that can be made simpler and cheaper right here.

Moreover, the tweet is a perfect tool to value the work of young researchers, the fruits of our work are not usually immediate and often society does not recognize the importance that the work of young researchers who are in Euskal Herria can have until a few years later. The Thyothesis gives us the power to socialize and make our work visible, to show our research to society. Mass-media and the media are often starred by researchers who publish in journals as important as Nature or Science, and works that may be more humble but important do not often have access to society. It is precisely this vacuum that fills the Thyothesis.