Bioengineered kidney works in the body!
A rat shared a kidney with a human
Nadezhda Markina, Newspaper.roo
To make a kidney suitable for transplantation, scientists had to deprive it of its own cells and populate the renal framework with other cells. The rat test was successful: the kidney filters blood and produces urine. Although so far the bioengineering body is not up to the usual in terms of the quality of work.
The kidney is transplanted more often than all other organs: transplantation is the only radical way to cure a patient with renal insufficiency. Hemodialysis, that is, the purification of blood outside the body, is only a temporary solution to the problem, before receiving a donor organ. There are about one million patients with such a diagnosis in the USA, and about 100 thousand people are diagnosed with it every year. 100 thousand patients are waiting for a donor kidney, and only 18 thousand receive it annually. In the kidney waiting list, the annual mortality rate is 5-10%.
The lack of donor organs is the first problem of transplantology. The second problem is that people with a transplanted organ need to take immunosuppressants for life to suppress immunity and, accordingly, be at risk of various diseases. 20% of patients still have episodes of acute rejection of the donor kidney within 5 years after transplantation. 40% die or lose the function of the transplanted kidney within 10 years after transplantation. Creating a bioengineered kidney suitable for transplantation will save many lives.
In the field of creating bioengineered organs, two fundamentally different directions are developing: one is based on the possibilities of 3D bioprinting of tissues and organs, the other is based on the use of natural or synthetic scaffolds that are seeded with stem cells. Scientists of the Massachusetts General Hospital (Massachusetts General Hospital) went the second way. They created a kidney from the skeleton of a rat kidney, which they populated with the corresponding rat and human cells.
A bioengineered kidney was transplanted into the rat's body and its operability was verified. The researchers published the results of their work in the journal Nature Medicine (Song et al., Regeneration and experimental orthopedic transplantation of a bioengineered kidney). The transplanted kidney performed all its functions: passed blood through the vessels, filtered, absorbed and excreted urine.
"What is unique in this approach is that we completely preserved the architecture of the organ, so that the bioengineered transplant was virtually no different from a donor kidney and was embedded in the circulatory and excretory systems," said Harald Ott, an employee of the Center for Regenerative Medicine at the Massachusetts Clinic, the first author of the article.
First, scientists took a rat kidney and completely removed the cells from it. This operation, decellurization, is performed by perfusing (washing) the organ with a detergent solution that washes out the cells. As a result, they received a kidney skeleton devoid of cells, consisting mainly of collagen, completely preserving the structure of the organ. What is very important, the microstructure of the main elements of the kidney – nephrons, consisting of a renal body with a glomerulus of capillaries inside and a system of tubules, was preserved.
After removing all living cells from the rat kidney, a collagen skeleton remains, ready for colonization with kidney and vascular cells (pictures and video – from the press release of MGH Researchers develop implantable, bioengineered rat kidney - VM.
This framework was populated with new cells, and several types of cells had to be used to construct a full-fledged kidney. Cells of the endothelium (inner wall) of human blood vessels and cells of the renal epithelium of a newborn rat were taken. In order to place them in the right places, endothelial cells were delivered by injection through the renal artery, and renal epithelial cells were injected through the urethra. Microstructural analysis showed that with this method of delivery, cells of the first type populated blood vessels and capillaries inside the glomeruli, and cells of the second type were fixed in the renal corpuscles and tubules. After that, the kidney matured in the bioreactor for 12 days.
The finished bioengineered kidney was tested for operability. First, blood was passed through the kidney in vitro, outside the body (in the picture on the right – VM). As a result of filtration and reverse absorption of water and nutrients, the kidney formed urine. Then the scientists tested the kidney in vivo – transplanted a bioengineered organ to a rat with its own kidney removed. The operation was successful, the kidney was connected to the circulatory and excretory system. Once in the body, the kidney began to perform its function and secrete urine.
The researchers evaluated the work of the kidney by several parameters – the rate of blood filtration, the release of creatinine (the product of protein breakdown), the reverse absorption of glucose and electrolytes. So far, the authors write, according to all indicators, the function of a bioengineered kidney is reduced compared to a conventional donor kidney.
As they believe, this may partly be due to the immaturity of the cells of the newborn rat, with which the carcass was sown. In the future, they are going to grow cells in culture until they mature and thereby achieve a functionally complete bioengineered kidney.
"If this technology turns out to be applicable to the size of a human kidney, patients suffering from kidney failure who have been waiting for a donor kidney for many years will receive an alternative – a bioengineered kidney populated with their own cells," says Harald Ott. A step towards this has already been taken: the researchers subjected a kidney taken from a deceased pig and a kidney taken from a deceased person to the decellurization procedure.
The procedure was successful: they managed to obtain a human kidney skeleton while preserving its microstructure. Now scientists are studying methods for obtaining the right types of cells from a patient and growing them in culture in the amount necessary for seeding a human-sized frame. Ideally, the frame should be seeded with the patient's own cells, which will completely eliminate organ rejection. So scientists hope that over time, a bioengineered kidney will be able to completely replace a donor kidney (for transplantation to patients with renal insufficiency).
Portal "Eternal youth" http://vechnayamolodost.ru15.04.2013