Anthony Atala (Peru, 65 years old) is a surgeon, urologist and bioengineer, perfect areas of knowledge to combine in regenerative medicine research. Arriving in the United States from his native Peru at the age of 11, Dr. Atala today directs the Wake Forest Institute for Regenerative Medicine (North Carolina), and is a professor and director of the Urology department at the university of the same name. Sixteen technological applications developed in his laboratory have already been used clinically in humans. Member of the most relevant science academies and holder of numerous awards, he is known for being one of the first organ bioprinters: with various materials and human cells he reconstructs tissues and organs that he implants in humans. That is basically the definition of regenerative medicine. Invited by the Social Council of the University of Granada, Professor Atala visited the city last week and gave a conference. He has also responded to EL PAIS.
Ask. What is regenerative medicine? When did people start talking about it and when did it establish itself as its own line of research?
Answer. The origin of this medicine begins in the first decades of the 20th century, with Alexis Carrel, a Frenchman who began cultivating organs at the Rockefeller Institute in New York. And he did it together with Charles Lindbergh, the first aviator to cross the Atlantic, who collaborated with him as a mechanical engineer. In 1935, both built the first perfusion pump – an instrument to keep organs removed from the body irrigated and functioning. With them began the possibility of extracting organs and keeping them alive outside the body. In 1954, the first successful organ transplantation took place in Boston, led by Joseph Murray, who would later become a Nobel Prize winner: a kidney transplanted from one twin to the other. From there, and linked to cancer treatment, comes the concept of cell transplantation. The treatment of skin cells in burns, in the 80s, is another important step. The skin is not grown yet, but the cells do improve the wounds. It is the beginning of tissue engineering. Regenerative medicine did not arrive as such until this century. This medicine combines all of this, cell transplantation, the manufacture of support structures, tissue growth and allows the regeneration of damaged organs or, better, parts of them.
Q. Will regenerative medicine allow us to live longer and better, only better, only more?
R. Vital organs such as the uterus, heart, kidney, do not have an expiration date. Theoretically, they are prepared to function for many years without fail. So, although in practice they can cause problems, if they don’t, regenerative medicine doesn’t offer you more years of life, it doesn’t prolong it. This medicine will make it possible to replace tissues and organs if necessary. If that regeneration refers to organs that do not affect longevity, it will not make you live longer, but it will make you live better. If the regeneration affects vital organs, of course, we will live longer. One quality of regenerative medicine is that it returns the organs to their original state and does so with their own cells, which avoids many problems.
In fact, a report from various US government agencies states that regenerative medicine will be the predominant force in the medicine of the future.
Q. This week, a woman in Barcelona gave birth to a son with a transplanted uterus. Would it be possible to give birth with an artificial, bioprinted womb, for example?
R. We have not tested it in humans yet but our studies indicate that it will be possible. We have been working on this for almost 20 years and we know that, by using the patient’s own cells, all of the patient’s natural functions can be reproduced. In short, it is an organ as yours as the original.
Q. What percentage of the human being could be replaced by artificial organs?
R. Theoretically, being own cells, all organs. Prostheses can cause rejection, inflammation. Someone else’s organs require immunosuppressive drugs your whole life and there is always the risk of rejection as they are foreign cells. In regenerative medicine the new organ is never rejected. The body thinks it is its own organ.
Q. What is the cell source?
R. They are the same organ that you want to build. If I want to make a kidney, I do a biopsy and take cells from that kidney, I expand them outside the body for 4 to 6 weeks. Then we build the support to which we incorporate these cells, either by hand or printed, and the patient can now be placed on it. That is the technique.
Q. How do cells know to become kidney, bladder, or skin?
R. Any cell has all the information necessary to replicate a person, as happened with Dolly the sheep. Then, depending on how they are made to grow, they become one type of tissue or another and are used for one organ or another.
Q. Who had the idea to think that those tissues that were made in a laboratory, outside the body, could be printed or, better, bioprinted?
R. The idea of printing DNA had been around for years, so printers have been designed for the medical field for a long time. Injection 3D printers also existed a long time ago. Everything comes from that concept. The difficult thing was to get structures that were really tissue. That required more technology than existed. So, we worked until we got what we have now.
Q. The important thing then is that bioink. What is it made up of?
R. It is nothing more than a liquid in which you include human cells. To manufacture this liquid we have up to 60 materials available. Then, depending on the case, we make a very liquid, gelatinous bioink, like a jelly bean. That liquid is really just the support for the cells that, over time, disappears.
Q. How does it disappear? What happens to that support?
R. With the printer, or when done by hand, we manufacture a structure in the shape of the organ that we are regenerating to introduce the cells in their place and with their shape. This support disintegrates over time, normally 6 months, which in the case of complicated organs with a lot of three-dimensional structure can take up to 18. The goal is that this structure is not permanent so that the body has exclusively its own cells. The mold –which, in any case, would not be rejected because it has no genetic content– must disappear because if it remains, we would already be talking about a prosthesis, something alien. The goal is that, as the support disappears and the cells feel that their scaffolding is being lost, they behave naturally and grow and rebuild their own support. That is regenerative medicine: the artificial support must disappear to, over time, leave only one’s own cells.
Q. Can the brain be regenerated like this?
R. Yes, we are already making small brains. However, a life-size human brain has yet to be made. There is a lot left, but in science you never say never.
Q. Are there tissues or organs more difficult to regenerate than others?
R. They are all complicated but flat tissues, such as skin, are the least difficult. Then there are the tubular tissues through which air or liquid passes. Next, non-tubular hollow tissues, and finally, the most complicated are solid organs such as liver, kidney, heart, etc. The great difficulty of these is the need to have them nourished vascularly. This vascular network in solid organs is very difficult to reproduce. But now, at different levels, we are able to reproduce all four types.
Q. In the United States there is 10 times more need for organ transplants than available organs. Is this bioprinting and regeneration a solution? When will it be regularly available?
R. It is one of the solutions. In science we never say no but we never say exactly when either. In the United States, different types of tissues, smooth, tubular and hollow, are already being regenerated in humans. Regarding the organs, on the other hand, we are only doing partial replacements. We do this because the body actually has a reserve of about ten times what it needs. This means that many organs fail when they are at 90% failure. Only when this leaves the organ below 10% of its functionality is when it becomes noticeable, for example, a heart attack, kidney failure, etc. For this reason, we can do partial organ replacements and that is what we are doing with the kidney cells, restoring a percentage of the kidney, enough for the patient to live comfortably. Now we are working on about 40 different tissues and we have done 16 different types of treatments, but there is still a long way to go.
Q. What is more difficult, the investigation or the subsequent adaptation to the regulations?
R. One of the challenges of our research is that the advances are safe for patients. It is what the regulation also seeks, so we cannot be against it. It is true that, in some cases, like any process carried out by humans, it is stricter than others and depends on who is on the other side. With regulation, as with other things, you have to be sure that the product is safe and that it works for the patient. The rest is adapting to the procedure and knowing how it works. It must be taken into account that the average regulation of a technology is 14 years and that after another few years, doctors become familiar with these new techniques. Being a researcher is also being very patient.
Q. Are the EU and US regulations in this area different?
R. They are very similar, really. If in the United States we need a product from Europe, it is accepted without problems and vice versa as well.
Q. The next step to bioprinting is the body-on-a-chip (the body on a chip). What is it about?
R. This has its origin in regenerative medicine technologies. It is about printing different organs the size of the head of a pin using the technology that we have talked about support and cells. We embed these different organs, up to twelve, in a microchip and using the appropriate sensors we reproduce the real behavior of the different organs and their relationships with each other. Thus, for example, we can speed up times as far as the safety of medicines is concerned. An example: 90% of the medicines that pass the first phase of clinical trials with humans never reach the market, but to get there, it has taken a lot of effort and money and many years. Decades and maybe hundreds of millions of dollars. This great failure is due to the fact that pharmaceutical companies use 2D tissue replica models – when the human body is 3D – or animal models that are not exactly like humans. With these organs-on-a-chip, created in 3D from human cells, we exactly replicate the originals in shape, texture, behavior, etc. Thus, in a couple of weeks we can verify more accurately what traditional methods verify in years, the safety of a drug, its influence on each organ and how the organs react together with the drug. All this speeds up the process of discovering the positive and negative effect of drugs. It’s a mix of regenerative medicine, microchips and biosensors.
Q. Is regenerative medicine implanted in hospitals?
R. He is slowly adjusting. Certain hospitals are already working on the regeneration of skin tissue.
Q. Will it be possible, or necessary, for each hospital to have a regenerative medicine unit or will production centers have to be established and distributed from there? Are you thinking about transportation and care?
R. This is, finally, an industrial process, with a specific protocol and they will have to be manufactured in specific areas. The hospital will take a biopsy, which will be sent to the production facility where the tissue or organ will be made, and returned to the hospital. There, the good news is that the surgeon doesn’t need to learn anything he doesn’t already know to implant the new tissue. For this reason, another issue that we work on is transportation and our clinical trials take this into account.
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Source: EL PAIS