Full-fledged bones from stem cells
Functional bone tissue was obtained from human induced pluripotent stem cells
LifeSciencesToday based on NYSCF materials:
NYSCF scientists create personalized bone substitutes from skin cellsA group of scientists from the Research Institute of the New York Stem Cell Foundation (New York Stem Cell Foundation (NYSCF) Research Institute) reported on obtaining bone substitutes from skin cells suitable for eliminating large bone defects.
The study, led by Darja Marolt, PhD, and Giuseppe Maria de Peppo, PhD, published in the Proceedings of the National Academy of Sciences, is a significant step forward in the development of personalized reconstructive treatments for patients with bone defects resulting from illness or injury.
This achievement will facilitate the on-demand cultivation of three-dimensional bone grafts that precisely match the needs and immune profile of the patient. To return adult skin cells to a state close to that of embryonic stem cells, NYSCF scientists used advanced "reprogramming" technology. Induced pluripotent stem cells (iPSCs) obtained from mature differentiated cells carry genetic information identical to the patient's genetics and can become a cell of any tissue of his body.
The scientists directed the development of induced pluripotent stem cells into bone-forming progenitor cells and seeded them with a substrate that allows to obtain a three-dimensional bone. Then this design was placed in a bioreactor, which, imitating natural conditions of development, provides cells with nutrients, removes slags, and stimulates cell maturation.
"Bone is more than just a hard mineral composite; it is an active organ that is constantly being remodeled. Blood vessels supply important nutrients to healthy cells and remove waste; nerves provide communication with the brain, and bone marrow cells form new blood cells and the immune system," explains Dr. Marol.
Previous studies have shown the possibility of bone tissue formation from other cellular sources, but scientists are aware of the dangers associated with their use in the clinic. The stem cells of the patient's own bone marrow can form bone and cartilage tissues, but not the vascular and neural networks associated with them, and the bone obtained from embryonic stem cells is at risk of rejection by the immune system. Therefore, in order to overcome these limitations, NYSCF scientists decided to work with induced pluripotent stem cells.
"No research group has yet published reports on the creation of fully viable, functional three-dimensional bone substitutes from human induced pluripotent stem cells. These results bring us closer to achieving our ultimate goal of developing the most promising methods of treating patients," says Dr. de Peppo.
Currently, bone defects and injuries are treated with bone grafts obtained either from other bones of the patient himself or from the material of donor banks. Synthetic bone substitutes are also used. None of these technologies makes it possible to achieve a comprehensive reconstruction. In addition, such grafts can cause immune rejection and are not always able to fully integrate into the surrounding connective tissue. For patients with shrapnel wounds or injuries sustained as a result of a car accident, these traditional methods of treatment provide only limited restoration of function and cosmetic effect.
After a comprehensive in vitro analysis of the obtained bone, NYSCF scientists addressed one of the main problems associated with iPS-cell-based therapy and assessed its stability during transplantation into an animal organism. Undifferentiated pluripotent cells can form tumors called teratomas. Bones obtained from partially differentiated progenitor cells were implanted under the skin of mice with weakened immunity. After 12 weeks, the structures matured and showed no signs of carcinogenesis; throughout the fully matured bone grafts, the integration of blood vessel cells into them began. These results prove the stability of bone substitutes.
Human skin cells were reprogrammed into induced pluripotent stem cells. With the help of chemical additives, stem cells were reprogrammed into bone progenitor cells, which were placed on a collagen substrate for growth. Fragments of the grown tissue were implanted into the mouse body, which recognized them as bone. Blood vessel cells began to migrate to the implanted tissue.
Scientists warn that, although these results are an important step forward, further research is needed before skin-derived bone grafts can be used in the clinic. The next steps will include optimizing the protocol and research aimed at achieving successful bone germination by blood vessels.
"Based on these results, we will be able to create personalized bone grafts for patients on demand without the risk of rejection by the immune system," says NYSCF CEO Susan Solomon. "This is not a good approach, it is the best approach to repairing destructive damage or defects."
In addition to the potential therapeutic significance, adaptive bone substitutes can be used as models of bone development and various bone pathologies. The analysis of these models will enrich today's understanding of both normal and pathological processes and will help in the identification of potential drugs.
Article by de Peppo et al. Engineering bone tissue substitutes from human induced pluripotent stem cells is published in PNAS.
Portal "Eternal youth" http://vechnayamolodost.ru08.05.2013