Instead, signaling molecules and proteins induce cells to differentiate into a particular type, normally based on need. Erythropoietin (sometimes called Hematopoietin) induces red blood cell formation by preventing proerythroblasts from entering the apoptosis pathway. Erythropoietin is both sufficient and necessary for promoting this fate. Similarly, Thrombopoietin induces the megakaryocyte differentiation pathway to yield thrombocytes. The factors alter the fate of HSCs and produce target cells according to need. For example, Thrombopoietin is more highly produced when platelets are in low supply or when more are needed for a blood clotting response.
Future Research and Therapeutic Application
The value of adult stem cell research, and more specifically HSC research, cannot be overstated. HSCs hold significant value in particular, as they can become any kind of blood cell type. The use of artificial factors to promote a particular fate may offer targeted approaches to tissue regeneration. Inducing differentiation into lymphocytes could prove to be therapeutic in those who are immunocompromised.
Inducing differentiation into erythrocytes could prove to be therapeutic in those who have a reduced oxygen carrying capacity. Harvesting stem cells for transplantation is not a new phenomenon, and thousands of lives have been saved as a result of bone marrow transplants. Less invasive methods of extraction, such as use of HSCs circulating in the blood, could improve transplant outcome and quicken recovery time. Artificial hematopoiesis could create blood that would solve the problem of shortages in blood banks. Future work could investigate the potential for HSCs to become cells of other tissue types, as current research has already shown that they can become hepatocytes. The broad versatility of HSCs has and will continue to bring them to the forefront in modern stem cell research.
Krishna S. Vyas
Sibi Rajendran
University of Kentucky College of Medicine
See Also: Blood Adult Stem Cell: Current Research on Isolation or Production of Therapeutic Cells; Blood Adult Stem Cell: Development and Regeneration Potential.
Further Readings
Domen, J. and I. L. Weissman. “Hematopoietic Stem Cells Need Two Signals to Prevent Apoptosis; BCL-2 Can Provide One of These, Kitl/c-Kit Signaling the Other.” The Journal of Experimental Medicine, v.192/1 (2000).
Duong, H. K., et al. “Peripheral Blood Progenitor Cell Mobilization for Autologous and Allogeneic Hematopoietic Cell Transplantation: Guidelines of the American Society for Blood and Marrow Transplantation.” Biology of Blood and Marrow Transplantation (2014).
Kelley, L. L., W. F. Green, G. G. Hicks, M. C. Bondurant, M. J. Koury, and H. E. Ruley. “Apoptosis in Erythroid Progenitors Deprived of Erythropoietin Occurs During the G1 and S Phases of the Cell Cycle Without Growth Arrest or Stabilization of Wild-Type p53.” Molecular and Cellular Biology, v.14 (1994).
Mazo, I. B., S. Massberg, and U. H. von Andrian. “Hematopoietic Stem and Progenitor Cell Trafficking.” Trends in Immunology, v.32/1 (2011).
Shizuru, J. A., R. S. Negrin, and I. L. Weissman. “Hematopoietic Stem and Progenitor Cells: Clinical and Preclinical Regeneration of the Hematolymphoid System.” Annual Review of Medicine, v.56 (2005).
Weissman, Irving L. “Stem Cells: Units of Development, Units of Regeneration, and Units in Evolution.” Cell, v.100/1 (2000).
Bone: Cell Types Composing the Tissue
Bone: Cell Types Composing the Tissue
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Bone: Cell Types Composing the Tissue
The skeletal system is the internal framework of the body that serves for protection, support, movement, production of blood cells, storage of ions, and endocrine regulation. Bone is a highly vascularized and mineralized connective tissue that is also a dynamic tissue that constantly undergoes structural reorganization. Bone is composed of cells, fibers (such as collagen), and amorphous ground substance.
Bones have many different roles in the body, as evidenced by the different types of bone and the different types of cells within them. Mature bone is mainly shaped and composed by three cell types: osteoblasts, osteoclasts, and osteocytes. Osteoblasts and osteoclasts can be thought of as having complementary building and destroying functions, respectively, whereas osteocytes serve more of a maintenance function. Inside the sheath formed and maintained by these cells is bone marrow. Bone marrow contains stem cells that develop into immune cells and red blood cells, along with cells that maintain the mineralized bone.
Osteoblasts
The main function of the osteoblasts is to secrete the organic components of bone, collectively called osteoid. Osteoid consists partially of type 1 collagen fibers, which are deposited by the osteoblasts in different orientations, giving bone its tensile strength. Also secreted by the osteoblasts is chondroitin sulfate, a type of glycosaminoglycan (GAG) and the primary component of the ground substance of bone. GAGs are sugars that attach to proteins as part of a proteoglycan. In the case of bone, chondroitin sulfate strengthens the protein matrix, giving bone its resistance to compressive stimuli. In addition, osteoblasts secrete hydroxyapatite, a hard calcium-based salt that mineralizes the previously secreted organic matrix. This mineralization gives bone further resistance to compression. Osteoblasts also secrete alkaline phosphatase to create sites for calcium and phosphate deposition, which allows for bone mineral crystals to grow at the site, become mineralized, and form bone. Alkaline phosphatase is present on the osteoblast surface until they either differentiate into osteocytes or bone lining cells. Bone lining cells are inactive osteoblasts that line the surface of all the bony spicules of spongy bone. Once activated, they become osteoblasts and deposit new bone. Their retraction and exposure of the surface of the bone matrix initiates resorption of bone in the dynamic process of bone remodeling.
Osteoblasts communicate using their cytoplasmic processes in a cellular organization called a syncytium. As osteoblasts are continually secreting osteoid around them, they often become surrounded by their own secretion, at which point they are known as osteocytes. Alternatively, osteoblasts can cover the surface of the bone as bone lining cells. Bone lining cells are essentially inactivated osteoblasts and can be reactivated to continue their secretory function. They also play a role in osteoclast recruitment as they cover and uncover the surface of the bone.
Osteoclasts
Osteoclasts are large cells that perform a complementary function to osteoblasts. Derived from a fusion of multiple precursor monocytes (uninucleated cells that can differentiate into various phagocytic cells), osteoclasts are multinucleated and phagocytotic (they possess the ability to ingest and degrade extracellular substances).
Each osteocyte has two surfaces: a smooth surface facing away from the bone and a highly evaginated/ruffled or active surface adjacent to the bone surface that increases the surface area for the secretion of hydrolytic enzymes for digestion of amorphous/inorganic/mineralized bone, leaving exposed the organic collagen fibers. Due to the many secretory granules, osteoclasts must maintain many vesicles (a cell storage organelle), which they secrete through their ruffled border.
When activated, an osteoclast has the ability to secrete hydrolytic enzymes and acid, which can degrade the mineralized organic matrix deposited by osteoblasts. The resorbed portion of the surface of the bone is termed a Howship’s lacunae and is separated from space outside the bone by attachments of the osteoclast’s plasma membrane to the peripheral bone. This belt-like seal between the two surfaces is termed the sealing zone, which compartmentalizes the working area of the osteoclast so that the digestive processes can be controlled. The sealing zone has actin filaments that attach to osteopontin in the mineralized bone surface through integrins.
Osteoclast activation and action are regulated by two main hormones: