alt="Image 11"/>
Bone marrow examination of cells with Wright’s stain showing neutrophil precursors. Promyelocytes are shown in the middle, two metamyelocytes are next to it, and two band cells and segmented neutrophils are at top left. Progenitor cells have the capacity to become megakaryocytes, erythrocytes, mast cells, and myeloblasts. (Wikimedia Commons)
The second common class of progenitors is the lymphoid progenitor cell type. These cells give way to all lymphocytes, along with Natural Killer (NK) cells. B lymphocytes mature in the bone marrow, whereas T lymphocytes mature in the thymus. B cells can also further differentiate into antibody secreting plasma cells. NK cells are cytotoxic lymphocytes that can recognize infected cells without the assistance of antibodies. Lymphoid progenitor cells thus play a critical role in the adaptive immune system, the system that keeps memory of foreign pathogens.
Target Cells and Inducible Fates
It is over-simplistic and incorrect to say that each HSC can form one final differentiated cell. Cell divisions occur in various cell-type intermediates, influencing the final number of target cells. For example, a starting multi-potential HSC, if choosing the erythrocyte pathway, first differentiates into a myeloid progenitor and then a proerythroblast.
The proerythroblast differentiates into an erythroblast, and the pathway continues to normoblast, reticulocyte, and finally erythrocyte. Each of these intermediate cell types also divides at least once, creating many erythrocytes from one proerythroblast. These mitotic divisions are necessary to meet the high demand of specific blood cell types. Through a modified endomitotic mechanism, one megakaryocyte produces thousands of platelets. Modifications and divisions become very necessary to produce enough of the needed target cell.
Differentiation is not a random process. 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
113
115
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
