Artificial heart grown from human cells on a mouse frame
The humanized heart of a mouse
Polina Rozentsvet, <url>More than 17 million people die from cardiovascular diseases every year.
In the United States alone, heart disease takes one human life every 34 seconds, and more than 5 million Americans suffer from chronic heart failure. Many patients can be saved only by heart transplantation, but it is impossible to find donors for all. Regenerative medicine and tissue engineering offer a way out: instead of selecting donor organs, they need to be grown in the required quantity.
Specialists of the University of Pittsburgh Faculty of Medicine suggest using progenitor cells obtained from the patient's fibroblasts and a three-dimensional skeleton of a real heart for this purpose.
In an article published in the journal Nature Communications (Lu et al., Repopulation of decellularized mouse heart with human induced pluripotent stem cell-derived cardiovascular progenitor cells), scientists described the first successful experiment conducted on a mouse heart: it was deprived of its own cells and populated the collagen base with human cells. A chimeric heart has grown, which cannot yet replace the present, but is capable of contracting.
The technology of growing a heart on a frame is being developed in different laboratories. In particular, they experiment with pig or rat hearts, but at the same time they use animal cells. Researchers from Pittsburgh for the first time used multipotent human cardiovascular progenitor cells – MCP (see the press release Decellularized Mouse Heart Beats Again after Regeneration with Human Heart Precursor Cells in Pitt Project - VM).
The term "multipotent" means that cells have multiple abilities to differentiate – they can turn into cells of different tissues. They are obtained from fibroblasts – connective tissue cells taken from a small piece of skin. With the help of various growth factors, fibroblasts are first converted into MCP, and then the development of MCP is directed in the right direction to obtain from them the cells that form the heart: cardiomyocytes organized into muscle fibers, endothelial cells (the inner wall of blood vessels) and vascular smooth muscle cells. The researchers used cultures from a collection of cells.
In order for the cells to form an organ, they need to be "settled" in a three-dimensional frame. It can be made from artificial material, but it is preferable to use the natural basis of the corresponding organ, which retains its original shape and contains biologically active substances that stimulate cell differentiation and division. To create an artificial human heart, it is convenient to take the frame of a pig's heart, but the researchers, working out a new technology, chose a small, mouse-like one.
First, with the help of special enzymes and chemicals, all the heart cells were removed. This technology is well developed. After 10 hours, only a protein skeleton of collagen, fibronectin and laminin with intact walls of large vessels remained from the organ. In this "skeleton", the researchers injected a suspension of MPC through the coronary artery. The heart was irrigated with a nutrient medium with the necessary growth factors and cell dispersal and differentiation were observed.
After 20 days, a new heart grew — human cells on a mouse frame, with some kind of vessels. It spontaneously contracted at a frequency of 40-50 beats per minute and reacted properly to drugs that accelerate or slow down its rhythm. Unfortunately, there are not enough fibroblasts in the heart yet — it turned out to be too weak to pump blood effectively, but still it beats.
This is the first artificial organ derived from IPC. Researchers are going to improve the technique so that the heart contracts with sufficient force and has a normal conducting system that regulates the rhythm of heart contractions. There is still a lot of work, but scientists are making big plans. They hope to use a new model of regeneration to obtain fragments of heart muscle tissue and use these "patches" to replace areas of the myocardium that died after a heart attack. And, of course, in the future, to get an artificial heart grown from a piece of the patient's skin. But this is a more difficult task.
Portal "Eternal youth" http://vechnayamolodost.ru14.08.2013