Recipe for making kidneys
"We managed to make a miniature kidney"
A well-known specialist in the field of regenerative medicine –
about how to make a bioengineered kidneyLarisa Aksenova, Newspaper.
About the creation of a human mini-kidney, about the development of cellular biomedical technologies and prospects for cooperation with Russian scientists "to the Newspaper.Ru" was told by Anthony Atala, a world-famous specialist in the field of regenerative medicine.
90% of people who are waiting for a transplant need a kidney transplant, and only 35% of them can expect to receive a donor kidney within five years. And this means that many of those who could be saved are dying. Doctors pin certain hopes on regenerative medicine. And indeed, it is possible that in the next few years technologies will appear, thanks to which it will be possible to significantly improve the quality of life of such patients.
Regenerative medicine seems to be a young science that is being born before our eyes, but it has been counting down since 1938, when the book "Organ Culture" by Nobel laureate Alexis Carrel and Charles Lindsberg was published. Carrel developed methods of vascular transplantation, and together with Lindsberg, a perfusion pump that supports the viability of an organ outside the body during operations, for example, on an open heart.
For quite a long time, scientists could not approach the problem of creating artificial organs – because of the insufficient level of technology development. Over the past couple of decades, biocompatible materials with certain properties have been created, biologists have learned how to grow cells and tissues of the most important human organs in the right amount. But even today there are a number of problems that, despite significant successes, still cannot be overcome.
Anthony Atala is a practicing urologist, Head of the Department of Urology at Wake Forest Medical School, Director of the Wake Forest Institute of Regenerative Medicine, USA. He coordinates the work of more than 300 doctors and researchers; under his leadership, 10 new treatment methods have been developed that are approved for use in US clinics. Anthony Atala came to our country two years ago at the invitation of the organizers of the second international popular science festival of the Dynasty Foundation. In his speech, he talked about the latest achievements in the field of regenerative medicine. And the other day, Dr. Atala visited Moscow again, already at the invitation of the Russian Academy of Medical Sciences.
– The kidney is a very complex organ: filtration of harmful substances and products of blood metabolism, reabsorption of water, glucose and other molecules necessary for the body and, finally, secretion take place here. The kidney also performs a number of other important functions in the body. In this organ, renin (blood pressure regulator), erythropoietin, stimulating the maturation of red blood cells, are synthesized and converted into the bioavailable form of vitamin D. The hemodialysis system can replace a failed kidney for a while, providing filtration and isolation, but it cannot perform endocrine and secretory work instead of a diseased organ. It is clear that when creating a bioengineered kidney, all these parameters must be taken into account. Will such a kidney become a reality?
– We have been working on creating such a tissue for quite a long time and today we can already reproduce the structure of the kidney in miniature. We wanted to understand how to make not one structural element of this organ, but several at once. In the strategy of creating most tissues, it is taken into account that the cells already have a "genetic spatial instruction". We divide the reproducible structures of the human body into four "architectural" types: flat – for example, the skin; tubular – blood vessels; hollow organs – the bladder; dense, or solid, organs, which include the liver and kidneys.
We have already successfully transplanted the first three types of structures to patients and have achieved some success in this. But solid organs are the most complex. We are trying to create them, but so far none of them has been transplanted into the human body.
As for the bioengineered human kidney, so far only a prototype has been obtained in our laboratory. We have recently published the results of this work.
We managed to make a miniature kidney that produces urine and retains all the metabolic functions inherent in an ordinary kidney. We judge this by the levels of vitamin D and erythropoietin. In the bioengineered tissue of a miniature organ, both the structure and all the elements of the nephron are recreated.
But the problem is how to make a full-sized kidney. The larger the organ, the more blood vessels are required to supply it with blood. To date, this problem has not yet been overcome. We pin our hopes on the bioprinting method. Bioprinting is essentially 3D printing, where a "frame" is used, a decellularized matrix of an organ, into which, by analogy with ink from a cartridge, living cells enter. This creates a three-dimensional living structure.
– From which cells did you make a mini-kidney?
– Using a needle, we took a cross-sectional biopsy of a kidney of a living patient. The cells of the capsule and renal parenchyma from the cortical and cerebral layers got into this biopsy.
– And how are the renal pelvis and ureter recreated?
– We are creating an artificial urine collection system. At the moment it is an external mechanical device. Now the task is to find a way to connect the mini-kidney to the existing urine collection system in the body, as with a conventional transplant.
– How long does it take to grow one artificial mini-kidney?
– It takes six to eight weeks.
– What technical difficulties will have to be overcome in order to eventually achieve a successful transplant of this bioengineered organ to a person?
– We are simultaneously working on five strategies at once. The first is to create "cassette fabrics". This is very important, since most solid organs have a high margin of functional strength and finally fail if about 90% of their tissues are damaged. Therefore, we see an opportunity to improve the function of the damaged organ with the help of such small "cassettes". With the help of "cassettes" it will be possible to "complete" the organs, expanding their function. We already use this strategy for the first three types of structures mentioned above (flat, tubular and hollow structures). The second strategy is as follows: we take a donor kidney, according to a certain method, we wash out all the cells from it with solvents, and the remaining "skeleton" of the organ, the matrix, we sow with the cells of the patient's kidney. The third strategy is bioprinting.
The fourth strategy is to use cells for therapy. And it is the fourth strategy that is most promising and will pass clinical trials in the first place.
The fifth strategy is to force the kidney to regenerate on its own. We are working in parallel in these five areas. Within a year, the fourth strategy will already go into clinical trials. In experimental models, we have improved kidney function after cell injection, and also showed that damaged tissues of the diseased organ are restored. The FDA (US Food and Drug Administration) has given permission for clinical trials. Of course, there are legal and legal issues, but we plan to test this method of treatment on patients within a year.
– There is a lot of talk about the fact that stem cells have a teratogenic effect, can cause cancer. How do you ensure the biosafety of the material used?
– Embryonic stem cells and cancer cells have in common the fact that they can be called "wild". These cells easily get out of control. We use cells from the organs of the patients themselves, because they are more stable.
We subject them to a full screening. The most rigorous screening, so that no cancer cell gets into the biomaterial.
– Please explain: are you forcing already differentiated cells to divide?
– In any organ of an adult there are cells with a sufficiently high morphogenetic potential. They are called differently: progenitor cells, dormant, progenitor stem cells. They carry certain biochemical markers that determine their further specialization into a specific type of tissue. Progenitor cells are capable of dividing, but to a lesser extent than early stem cells. During a biopsy, we select all types of cells, and then sort out the progenitor ones from them, already directed in their further development. In the professional environment, we call them "baby cells", but they are not fetal or embryo cells. People should not confuse them with embryonic ones.
– Are there such cells in any organ of any person?
- Yes. And they retain the ability to divide even, for example, in a 70-year-old person with kidney failure.
– Does your second visit to Moscow involve establishing scientific contacts, establishing cooperation with Russian doctors?
– We are looking for opportunities for cooperation with Russia and we see interest in our technologies, people want to master them. And we, in turn, want these technologies to be available everywhere.
– Are we talking about any specific developments? And how will the use of these technologies be regulated by law?
– We want to establish cooperation in terms of bioengineered flat and tubular tissue structures and tissues of hollow organs. In every country there is a question of technology registration, it will arise in Russia. There is a significant difference in regulatory issues, so we want to cooperate with different countries in order to implement our technologies faster.
– Do you assume the function of an intellectual center of such technologies?
– We started developing bioengineering technologies from the urinary system, since this is my clinical specialty, but our institute is also working on the creation of other organs. We study more than 30 different tissues, cooperate with many scientific and medical institutions. We have 277 collaborations to our credit, of which 203 are in the USA, 74 are abroad. Almost all major universities in the world cooperate with us. Among the countries are Great Britain, Switzerland, Mexico, Portugal, Japan, Australia, Korea, Brazil, Greece, Canada, South Africa, China, Sweden and others.
– And Russia?
– I hope that Russia will become the 75th country in our community.
– Have you been approached with such a request or was it an initiative of the Wake Forest Institute of Regenerative Medicine?
– Yes, I was approached with such a request. I can say that the negotiations were successful, and I am generally satisfied with the results of the trip.
– And the last question. What areas of regenerative medicine, in your opinion, are the most relevant?
– Of course, it takes a lot of effort to get the organ to regenerate on its own. We use small molecules and proteins to guide stem cells on the path of specialization. If it were possible to ensure that the damaged organ could restore its tissues on its own, the most important goal of regenerative medicine would probably be achieved.
Portal "Eternal youth" http://vechnayamolodost.ru13.06.2013