Stem cells in urology
It is also a landmark event in the world of relevant science, indicating, as it is customary to say now, trends.
In this regard, the 2012 prize in the field of physiology and medicine (by the way, it is more correct to call it the prize in physiology OR medicine – that's what it is called in English), awarded to John Gurdon and Shinya Yamanaka, can be considered a classic. For it was awarded for work in a key area of modern science – work on cloning and stem cells. D. Gurdon was able to clone a frog from epithelial cells for the first time, and S. Yamanaka was able to obtain pluripotent stem cells from ordinary differentiated cells. A century ago, such things were even theoretically considered impossible.
Let's remember our favorite histologyWhat are stem cells (SC)?
This is a source of renewal of all cells of the body, while a variety of cells can be formed from some types of SC. An embryo grows from stem cells. The first cell from which our body is derived is the stem cell. As well as thousands of subsequent cells. By the way, the existence of stem cells was predicted by the great Russian histologist and embryologist Alexander Alexandrovich Maksimov in 1908.
There are several types of stem cells. The most versatile stem cell is the zygote. It gives rise to all types of cells in the body. The same properties are possessed by blastomeres – cells formed during the first few divisions of the zygote. A whole organism can be grown from a zygote or a blastomer. Such cells are called totipotent stem cells.
Slightly less universal are the cells formed during several subsequent germinal divisions (before separation into germ leaves). They can give rise to all the cells of the body, but not to the placenta, so it is impossible to grow a whole new organism from one such cell. These cells are called pluripotent stem cells (PSCs).
Multipotent stem cells have already been specialized – that is, those that can give rise to many cell types characteristic of the body, but not all. Multipotent cells are, so to speak, "more or less potential" – that is, they can give rise to more or fewer cell types. Multipotent cells also include some of the stem cells active in the adult body, which were mentioned above. The gradual differentiation of the descendants of multipotent cells leads to the appearance of oligopotent (giving rise to only a small number of cell types) and unipotent (giving rise to only one type) cells.
The use of stem cells in medicine began quite a long time ago and was conducted in two directions:
- injections of the corresponding stem cells into the damaged organ and
- attempts to grow tissue or an entire organ with subsequent transplantation to the patient.
The second way is good because a person actually receives a new healthy organ instead of a damaged or deceased one, while eliminating problems with the compatibility of the donor organ. In recent years, scientists have grown many types of tissues and organs – from a heart valve to a whole heart. However, the latter does not work yet.
Urology did not stand aside either.
From a bladder from a test tube to a kidney from a ...printer (!)The urological community in 2006 blasted the message of Anthony Atala's group from North Carolina.
It turns out that E. Atala transplanted a bladder grown using stem cells to several patients back in 1999, but did not publish the results then in order to make sure that the operation was successful in the long term. Since then, about 30 similar operations have been carried out in the world.
Now E. Atala is one of the world leaders of a new direction in medicine, which has been called tissue engineering. In his laboratories, work is underway on the artificial production of a variety of tissues and organs, not only urological (despite the fact that E. Atala is the author of a large work Stem Cell in Urology, published in 2008). Cartilage, bones, vessels, urethra and many other organs and tissues are grown here.
They are also trying to "work" on kidneys, which are much more difficult to grow than a bladder. Professor Atala himself has high hopes for 3D printing technology, through which the organ can simply be printed from the corresponding cell cultures. However, simpler cases of cellular insufficiency are being treated by injecting stem cells into a failing kidney.
Other scientists are trying to work with the "traditional" method: to grow a kidney. Not so long ago, a report was published about successfully grown renal tubules of the human kidney.
And Harvard specialists led by Harald Ott reported in April 2013 that they managed to grow a whole rat kidney and transplant it to a live rodent. In this case, the kidney of a deceased rat was used as a "skeleton", from which all cells except connective tissue cells were removed. The resulting kidney did not contain all types of cells, produced only a third of the normal volume of urine and processed creatinine 36 times slower than the "natural" kidney. But, nevertheless, it is a success.
The same Dr. Anthony Atala, who first grew and transplanted a human bladder, conducted another successful experiment in 2009, though not on humans. He managed to grow and implant the tissue of the cavernous body of the penis. It is not surprising that Prof. E. Atala and his team chose rabbits as experimental animals.
The experiment ended successfully: 12 operated rabbits were mated with females, as a result, four females became pregnant. If the technology can be transferred to humans, it will be a major breakthrough in the treatment of severe erectile dysfunction and a serious alternative to penile prosthetics.
Of course, no reviews and articles can replace the living opinion of a scientist who works in this field. One of the leaders of tissue engineering, who was the first in the world to transplant a bladder artificially grown from stem cells to a person, the same Dr. Anthony Atala, head of the Institute of Regenerative Medicine at Wake Forest University, kindly agreed to give a blitz interview specifically for the Digest of Urology. After a hard day of surgery, he took the time to answer a few questions that we sent him by email.
– What are the main priorities in the development of technologies related to the use of stem cells in urology?
– Stem cells from the bladder (muscle and epithelial) are clinically used to create a bladder and urethra, which are implanted in the patient. Projects currently undergoing preliminary clinical trials include the use of progenitor muscle cells to treat urinary incontinence and erectile tissue cells to replace it. In addition, scientists from the Wake Forest Institute of Regenerative Medicine are conducting clinical studies on the use of spermatogenic epithelial stem cell transplantation as a potential treatment for male infertility.
– When was the first artificial organ of the urinary system created? When was it first transplanted to a human? And what is the fate of this patient?
– Bioengineered bladder was first implanted in a patient in 1999. We reported long-term results in seven patients in 2006. The examination showed that bioengineered organs function in the same way as organs restored with the help of the intestine, but without a single side effect. These patients are still doing well.
– Have you performed similar operations since then? How many of them are located around the world? Can you talk about putting this experience into mass practice?
– After our pioneering work, we licensed the technology to a company that continues to conduct clinical trials. Our technology has not yet passed the FDA approval procedure, so it is not available outside of clinical trials.
– What are the stages of formation of a new organ, for example, a bladder? How long does it take?
– It takes about 6-7 weeks to create a bladder in the laboratory. This period of time begins with a small biopsy with the collection of cellular material, continues with the cultivation of cells and ends with the implantation of a new organ into the patient's body.
– Are there any differences in the case of kidney creation? Is it difficult to make a kidney? How long will it take?
– The kidney is a much more complex organ than the bladder, both in terms of the number of cell types (about 20) and density. We are exploring several ways to treat kidney failure – from using 3D printing to create an organ to injecting stem cells into an organ. The main problems with tissue engineering are ensuring an adequate supply of oxygen to cells after implantation.
– The Nobel Prize in Medicine in 2012 was awarded to Shinya Yamanaka, who received stem cells from ordinary somatic cells. Do you have any plans to repeat your experience with the bladder, but with the use of somatic cells as primary material?
– With our tissue engineering technology, it would be ideal to use the patient's own stem cells, since there will be no problems with rejection. When this is not possible, the solution is to use stem cells from another source.
– What global achievements in this field over the past 5 years do you find the most important?
– The development of bioprinting is very important, as well as, of course, the work of Dr. Yamanaka and other scientists in the field of induced pluripotent stem cells.
Portal "Eternal youth" http://vechnayamolodost.ru18.06.2013