Revolutionary Chilean center to research the generation of new tissues and the use of cells to treat patients

“The big question to ask ourselves as a country is: do we want to address the health of new generations with obsolete treatments or do we want the most advanced treatments? The answer is obvious, but to make it a reality we need centers that develop new techniques and treatments that include advanced cell therapy, tissue engineering and precision medicine,” says Maroun Khoury, director of the new IMPACT Center.

This was one of the four new scientific centers of excellence that received a millionaire funding from the National Agency for Research and Development (ANID) for five years, renewable for the same period.

The researcher from the U. de los Andes, the institution that promoted this “Interventional Precision Medicine Center for Advanced Cell Therapy” (IMPACT), says that a decade ago treatments were based on drugs. “But that has evolved into biological treatments, i.e., based on stem cells or antibodies. Those who are leading this trend are not the big pharmaceutical laboratories, but researchers at universities and startups,” Khoury explains.

And that is precisely what IMPACT will do, changing, in part, the way in which medical research is conducted in Chile. “The first change is that we decided that health is not something that only concerns biomedical experts. We recruited researchers from other disciplines such as engineers who were capable of developing devices and sensors, or experts in computer science and artificial intelligence,” he says.

“For that we partnered with other universities. The Catholic University, for the topic of artificial intelligence; the University of Chile, for the engineering area; the Catholic University of Valparaiso, for the topic of bioprocesses, and the technical campus of the University of La Frontera,” he adds. Abroad, they added institutes in the USA, Europe and Singapore, among others.

Their other differentiating factor was to focus on studying diseases that have a high social impact (such as joint or autoimmune diseases) and also deadly diseases (such as cancer).

The new center is based on four pillars or areas of research. The first is the development of biomedical treatments, including cell therapy and precision medicine. The second is the generation of biomaterials and the development of tissue engineering.

Its third line is the use of artificial intelligence and bioinformatics to develop new generation clinical solutions.

Finally, all these areas converge in a fourth, where this cutting-edge research will be developed until it reaches the stage of next-generation clinical trials. In other words, this research will be translated into treatments that really reach patients and not just remain in a paper. Mainly in perinatal diseases, osteoarticular diseases, cancer, mental health and pain treatment.

New therapies

One of the fields in which this center will make contributions to medicine is cell therapy and precision medicine. To this end, a fundamental part of its research is exosomes, tiny vesicles that are expelled by cells and serve to communicate with each other.

They can be modified in the laboratory to include “components” that cure diseases.

“The main mission of the exosome is intercellular communication, so they have information that can modify a cell. We can load them with molecules, chemical compounds, drugs or nucleic acid that serve to treat diseases, such as cancer,” says Dr. Francisca Alcayaga, principal investigator of the IMPACT Center and academic at the U. de los Andes.

Millions of modified exosomes are used to treat diseases. Some are injected into the bloodstream to treat systemic diseases such as metastatic cancer, but sometimes they work better if applied locally to the affected area, as in a treatment for osteoarthritis.

Another area of action of the center is precision medicine, which is based on the premise that the same pathology does not present itself in the same way in different people. “Lung cancer can have a different genetic origin in two patients and you can treat it differently and precisely in each of them, and not as something generic,” he adds.

An example of this is loading exosomes with drugs that if you administer them in a naked way, that is, like a conventional drug, generate many side effects because it is absorbed by different cells in the body. “But these exosomes or nanotransporters can be directed to specific tissues, so we can use a lower dose, which reduces the side effects,” says Alcayaga.

With this approach they are already moving forward to generate trials for osteoarthritis and to investigate the treatment of knee osteoarthritis, injecting these exosomes into the joint.

At the center they will also use these exosomes as biomarkers of disease, meaning that the presence of a specific molecule in them can give indications that the patient is suffering from a pathology.

“When an organ is diseased, the diseased cell also secretes exosomes with a ‘signature’ of disease. So you can monitor the exosomes circulating in your body to detect the onset of a disease, its progression or the response to treatment,” says Alcayaga.

At the center, they will use these biomarkers to detect depression and perinatal diseases.

Tissue engineering

Another line of research focuses on tissue regeneration. It will include research into new biomaterials, as well as the development of medical devices that allow these tissues to be generated inside the body. These are devices that enter with material and 3D print it inside the body, which has many more advantages than developing the tissue extracorporeally. They already have a device, in the prototyping phase, which allows “printing” these tissues inside the body.

Sensors will also be developed. “This will make it possible to measure the patient’s progress in bone-joint rehabilitation or the heart’s effort after recovery from heart disease,” adds Khoury.

The third area is the use of artificial intelligence applied in two fields: the automated generation of magnetic resonance images and their subsequent analysis to generate the diagnosis. “The generation of these images is highly dependent on the operator and the quality of the equipment. This can be automated with machine learning, so that a professional from Santiago can monitor the acquisition of these images in remote locations,” adds the researcher.

They will then delve into the analysis of bone and joint images, and of perinatal diseases.

Saving lives

The big problem in Chile, say both researchers, is that with funding from a Fondecyt or other smaller competitive fund all these therapies are tested in mouse models. “But we don’t want to save the lives of mice, and that’s why we have to scale up to test this first in larger mammals and then in clinical trials. That’s expensive, and centers like these can go forward at these stages,” says Khoury.

“By receiving long-term funding, as is the case with the center, you ensure that you can go all the way to the clinical trial,” says Alcayaga.

This is key, the researcher adds. “Think about how much research in Chile in the last 10 years actually reached the patient. It was very, very little. To achieve this, not only scientists are needed, but also to involve professionals from other areas and to disseminate among patients the need to generate trials in order to advance in Chile from general medicine to precision medicine.”

Recognized trajectory

The background of this center is the first laboratory for clinical trials that was developed at the Universidad de los Andes. In 2008, they performed the first treatment of a lupus patient who was injected with their own expanded cells in the laboratory.

In 2010 they created the company Cells for Cells, which works in cell therapy and regenerative medicine. They use donor cells taken from umbilical cord blood. The advantage is that from a single cord they can treat 200 patients without problems of incompatibilities, since the cells are “hidden” from the immune system.

Another milestone is the generation of a consortium financed by Corfo in 2013 and which is valid for 10 years. This focuses on research into joint diseases that are often disabling.

Author: Alexis Ibarra O. /  El Mercurio – Sección: Vida, Ciencia y Tecnología 

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