A breakthrough in the field of tissue engineering: a team led by an Israeli researcher succeeded in creating functional muscle tissue from embryonic stem cells
Merit Sloin
Embryonic stem cells have enormous medical potential. But even if scientists know how to completely control the differentiation process of the stem cells into nerve cells, muscle cells, heart cells or insulin-secreting cells, it is still not clear how they will function in living tissue. The reason for this is that in the tissue the cells are arranged in an organized structure and maintain mutual relations with each other. If you want to create tissue from the embryonic cells, it is not enough to direct their differentiation, but you must ensure that they organize together in a three-dimensional array and function as a single unit.
The field of tissue engineering, which has developed in recent years, provides an answer to this. The idea is to let the cells organize themselves on top of a biodegradable scaffold, composed of biological materials. The cells gradually organize on top of the scaffold and form tissue, and at the same time the scaffold gradually degrades and its place is taken by the finished tissue. For this, a specific cocktail of growth factors must be put together, which will cause the cells to differentiate into the desired tissue; to develop a biological scaffold from materials whose rate of degradation corresponds to the rate of differentiation and organization of the cells; And in the end to check if a functional tissue is indeed obtained. This is a complicated process, since the tissue consists not only of the cells responsible for its functions, but also of blood vessels that supply it with oxygen and nutrients. For the transplanted tissue to function over time, its blood vessels must make contact with the body's vascular system.
About two years ago, Dr. Shulamit Levenberg succeeded in creating for the first time an organized three-dimensional tissue from embryonic stem cells that were grown on a biodegradable scaffold. Levenberg, who was then studying at the Massachusetts Institute of Technology (MIT), did the research together with a team of researchers from the institute led by Prof. Robert Langer. She now belongs to the Faculty of Biomedical Engineering at the Technion, and in collaboration with the same team of researchers from MIT succeeded for the first time in creating muscle tissue with a network of blood vessels, which functioned well when transplanted into animals and even attracted additional blood vessels to it. The research is published today in the journal "Nature Biotechnology".
"One of the main problems in tissue engineering is feeding the transplanted tissue by creating blood vessels inside it," Levenberg says. "Our goal was to create a tissue with a network of blood vessels in it, transplant it into the body within an existing tissue and see if the blood vessel array does indeed improve the absorption of the tissue. We chose to work with muscle tissue. It is a tissue rich in blood vessels, which are necessary for the high metabolism of the muscle."
Levenberg and the team of researchers grew mouse muscle cells in the laboratory together with embryonic stem cells that were instructed to differentiate into endothelial cells - the cells of origin of the blood vessels. "In tissue engineering, it is difficult to grow different cells that are together in a mixture, because each type of cells needs its own conditions," Levenberg says. After they managed to "mix" the endothelial cells with the muscle cells, the researchers seeded the cell mixture on a scaffold composed of a biodegradable biopolymer. "Vessels developed from the endothelial cells, and thus we were able to obtain a 3D array of blood vessels within the muscle tissue," says Dr. Levenberg.
In the next step, the researchers added to the array of cells and the polymer additional embryonic cells, which have the ability to differentiate into the muscle cells that line the blood vessels and whose role is to stabilize the blood vessels. "Our hypothesis was that these cells stabilized the array of blood vessels that we created, and indeed it was. We saw that the number of blood vessels increased and they grew and remained in the tissue over time," Levenberg adds. "We did all this in the laboratory in cell cultures. The next step was to check if the tissue, which consists of the cocktail of cells and polymer, will function properly and survive for a long time even when transplanted into the living body."
Levenberg and her colleagues examined this question in mice and rats. In one group of mice, they implanted the cell array and polymer under the skin; in another group - between muscle fibers in the leg; In a group of rats, muscle tissue in the abdominal area was replaced with the polymer array. "In the three groups, we saw that in all the places where we implanted the engineered muscle tissue with the blood vessel array, the implant survived for a longer period of time compared to engineered tissue with only muscle cells," Levenberg says. "In all these places, there was an increased formation of blood vessels in the graft. The transplanted endothelial cells pulled blood vessels from the mouse into the graft, and in addition to that they formed active blood vessels themselves. About half of the newly formed blood vessels had blood flow and they connected to the blood vessels of the mice."
The success of the research in the creation of muscle tissue, in the creation of blood vessels within the tissue, in the creation of tissue from several types of cells and in the use of endothelial cells from embryonic stem cells, constitutes considerable progress in the field of tissue engineering. What are the uses? The research is still at its beginning, but in the future, Levenberg says, the goal is to transplant the engineered muscle tissue when there is a lack of tissue (for example, in cancer patients who have undergone treatments in which muscle tissue was removed) or in trauma situations - after a car accident, for example, when muscle tissue restoration is required.
They knew the stem cells
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