Sama-sama-sama
Stem cells self-organized and became a material for 3D bioprinting
Vyacheslav Gomenyuk, N+1
Scientists have developed a method for printing living tissues on a 3D bioprinter, which uses stem cells and one of their most important properties is self-organization. As reported in the journal Nature Materials (Brassard et al., Recapitulating macro-scale tissue self-organization through organoid bioprinting), stem cells of different tissues placed in favorable conditions self-organized and formed tissues that looked and functioned like full-fledged living tissues.
The formation of tissues in a living organism depends on intercellular contacts and the microenvironment of cells. In the process of development and vital activity, cells form an extracellular matrix around themselves – a part of the tissue that serves as a mechanical support and mediator of information for cells. The cells are located in the matrix (respectively, and in the tissue) in a spatial relationship characteristic of each organ. To get to the right place at the right time, cells express hundreds of receptors and chemicals that determine the nature of the interaction of the cell with neighboring cells and the matrix. Thanks to such interactions, cells self–organize - each cell knows where it needs to be in the tissue and what it needs to do.
Until recently, scientists were unable to grow large organoids (larger than a centimeter) using 3D bioprinting, because either the cells were too tightly attached to the medium and could not move, or the medium itself did not allow creating the necessary microenvironment. However, Matthias P. Lutolf and colleagues from the Federal Polytechnic School of Lausanne have developed a new 3D bioprinting approach that can solve these problems. The new method, which, among other advantages, allows microscopically working with the cell mass and directly observing the printing and growing process, uses the self-organization of stem cells as a basis for growing full-fledged organs and tissues. This approach allows you to repeat the natural processes of tissue and organ development.
To demonstrate the potential and versatility of the new method, scientists used human small intestine stem cells. The stem cells printed in a line were placed on a nutrient medium made of hydrogel with collagen, which is similar in properties to the extracellular matrix. In this environment, the cells moved easily and created a fibrous connective tissue structure around themselves, additionally turning the environment into a favorable microenvironment.
After a few days, the cells transformed into a whole and organized epithelial tube from 5 to 15 millimeters long, surrounded by a specific matrix, in which scientists found a tissue organization found in classical organoids of the small intestine. At the same time, scientists note, it was the nutrient medium and extracellular matrix that had a great influence on the formation of the intestinal tube, which created a favorable microenvironment for cell self-organization. It is noteworthy that intercellular self-organization leveled small printing defects (for example, cell adhesion).
Immediately after the printing process, the cells condense into a tightly packed line, and then, thanks to self-organization, differentiate into epithelial cells of the small intestine.
Scientists also managed to grow the epithelium of the mouse small intestine. At first, the stem cells were arranged in the form of a line, but after four to six days, thanks to the self-organization of cells, a lumen appeared in this line, which turned it into a hollow tube. After another day or two, crypts and villi characteristic of the epithelium of the small intestine were found in the tube, in which scientists found mature differentiated enterocytes, Paneta cells (protective cells that occur only in the small intestine), goblet-shaped and enteroendocrine cells. The entire tube reacted entirely to external stimuli – Paneta cells released bactericidal granules in response to chemical irritation, and all cells swelled under the action of forskolin. These reactions show that the new bioprinting method can produce engineered tissues with physiological reactions resembling those in living organisms.
In addition, endothelial cells printed on a mixture with vascular endothelial growth factor (VEGF) formed de novo capillary vessels. Due to favorable conditions (VEGF, loose medium), the formation of capillaries was triggered on a tissue scale, which led to the formation of a vascular network with a continuous lumen.
All these experiments show that specific local interactions that control the self-organization of a small cell block can spread to the tissue level and form tissues of different types: both endothelial and internal environment tissues. The use of the self-organization property of stem cells should be an important step towards the cultivation of tissues and organs in vitro, because in this case it will be possible to obtain functionally complete organs that can be used for transplantation or drug testing.
Portal "Eternal youth" http://vechnayamolodost.ru