25 September 2014

Stem Cell Heart Valve

Alexandra Bruter, <url>A new approach to the manufacture of artificial heart valves based on the use of induced pluripotent stem cells (iPS cells) was proposed in the work of American researchers published in the latest issue of The Annals of Thoracic Surgery (Simpson et al., Engineering Patient-Specific Valves Using Stem Cells Generated From Skin Biopsy Specimens).

The human heart has four valves. Normally, they open only in one direction and provide blood flow in the right direction. The tricuspid valve is located between the right atrium and the right ventricle. Venous blood enters the heart first into the right atrium, from there into the right ventricle, then the right ventricle contracts to throw blood into the pulmonary trunk – a vessel through which blood will go to the lungs to be enriched with oxygen.


The scheme of blood flow in the human heart

The tricuspid valve is designed just so that when the ventricle contracts, blood enters the pulmonary trunk, and does not return back to the atrium. Similarly, the mitral valve is arranged between the left ventricle and the left atrium. The oxygen-enriched blood coming from the lungs first enters the left atrium, from it into the left ventricle, and from there, when the ventricle contracts, it goes to the aorta. The mitral valve prevents blood from flowing back into the atrium. The aortic valve opens from the left ventricle into the aorta and prevents the reverse flow of blood from the aorta to the ventricle when the ventricle is relaxed. The pulmonary valve performs a similar function between the left ventricle and the pulmonary trunk. It was constructed from cells by the authors of the article.

Valve insufficiency can be congenital and acquired (after infectious endocarditis or due to rheumatism), as well as of varying severity. In some cases, only replacing the valve with an artificial one can help. If a child has to replace the valve, for example, with a birth defect, a problem arises. The child is growing, but the valve is not. According to the STS Congenital Heart Surgery Database, approximately 800 children need a valve transplant every year.

It is possible to make a valve that would grow together with the new owner only from living cells. At the same time, foreign cells are not suitable, because they will cause an immune response in the patient. Getting your own cells of any type has become possible thanks to the use of iPS cells. Genetic constructs are introduced into fibroblasts (skin cells), which reprogram them into pluripotent stem cells. Then, with the help of other genetic constructs, the synthesis of molecules in the cells is started, turning these cells into mesenchymal stem cells. Mesenchymal stem cells can no longer differentiate into all types of cells, but mainly into cells of muscles, joints, bones and adipose tissue, that is, tissues formed during embryonic development from the middle germ leaf – mesenchyme.

The authors hope that in the future it will be possible to use blood cells instead of fibroblasts, the production of which is not completely painless (you need to cut out a piece of skin).

In general, obtaining artificial organs and tissues for transplantation is a very hot topic in modern science. The first clinical trials of such a method, which we have already described, have recently begun. In these trials, a patient with macular degeneration was transplanted with a fragment of retinal epithelium obtained from iPS cells. It is very important that this experiment confirms the safety of the method, which has previously been confirmed in numerous animal experiments. There remains a danger that some cell has not ceased to be iPS and can still divide indefinitely. This is fraught with the formation of tumors. It is easy to monitor the processes in the eye and take timely measures, which is probably why such conditions are chosen for the first tests. If the security is confirmed, it will open the door to similar techniques. For example, heart valves made of iPS cells.

In addition to the source of cells, there remains the issue of maintaining the three-dimensional structure of the valve. To do this, the authors used cell-free matrix technology (we have already written about some other cases of its application). The matrix is a relatively rigid frame of an organ formed by an intercellular substance. It usually consists of collagen and other glycoproteins, proteoglycans and hyaluronic acid. You can take someone else's organ (for example, a pulmonary valve), which cannot be transplanted just like that because of immune incompatibility, wash out the cells of the previous host from it and populate with the cells of the future host. At the moment, researchers have managed to grow a new heart valve in the laboratory on the basis of such a matrix and iPS cells.

If such a method is used for prosthetics of the patient's heart valve, an organ transplant will actually be obtained, but without problems with immunocompatibility. In general, recently there is hope that technologies based on the use of iPS cells will solve some problems associated with the rejection of foreign tissues during transplants of various organs.

Portal "Eternal youth" http://vechnayamolodost.ru25.09.2014

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