Читать книгу The SAGE Encyclopedia of Stem Cell Research - Группа авторов - Страница 143

Adult (somatic) stem cells are undifferentiated cells and have been found to exist in small numbers in almost all tissues and organs, even the heart and the brain. Although their origin in some tissues is still under investigation, their primary function is to maintain and repair the tissues in which they are found. They have generated a lot of excitement because of their potential for transplantation, as their sourcing would not be controversial, like that of embryonic stem cells.

Blood stem cells, also known as hematopoietic stem cells (HSCs), were the first stem cells to be identified. They are located in the bone marrow of the femur, pelvis, the vertebrae, and the rib cage. They can also be extracted from peripheral blood, umbilical cord blood (UCB), and the placenta. These stem cells differentiate into all types of blood cells in the body; they may be required to produce more than 500 billion of these cells daily. This demonstrates the multipotency as well as extensive self-renewal capacity of the blood stem cells. HSCs are located in a specific “stem cell niche” in the bone marrow.

The stem cells may go through various stages, such as quiescence, self-renewal, differentiation, or apoptosis, with these processes being controlled by the internal environment of the cells themselves. Experiments have identified GRP94, an endoplasmic reticulum chaperone, as an intrinsic factor present in the HSCs, which is required to maintain them within the niche. It also plays a role in regulating early T- and B-cell lymphopoiesis. However, it is now suspected, according to the niche hypothesis, that the microenvironment of the niche also plays a role in the maturation of the HSCs. In fact, the latest research suggests that bone cells (osteoblasts and osteocytes) may not only regulate the microenvironment of the niche but also modulate immune cell differentiation.

It is now possible to induce these stem cells to move into the bloodstream, from where they can be easily harvested and genetically modified. This strategy has been successfully used for the treatment of severe β-thalassemia, in which up to fourfold enrichment of HSCs was achieved. Peripheral blood stem cell mobilization was achieved by granulocyte colony-stimulating factor, followed by CD34⁺ HSC harvesting and lentiviral transduction, and eventual transplantation for the treatment of β thalassemia.