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Open Access Identification of Molecular Mechanisms Inducing the Activation and Ageing of Hematopoietic Stem Cells

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Medicine cannot yet take a stem cell line and grow whatever tissue we desire and furthermore, much like blood transfusion or organ transplants, using stem cells derived from a different individual is complicated by each person's unique immune system.
Untangling these webs is painstaking work but the reward is potentially great and this is what drives many to continue. Dr Takafumi Yokota and his colleagues at the Department of Hematology and Oncology at Osaka University Graduate School of Medicine are an example of this drive to continue as they have been working on a single particular type of stem cell for over 20 years. They do so because they believe this effort could pay huge dividends for research in treatment of blood disorders, aging and in the emerging field of regenerative medicine.
Yokota's work has been the study of authentic hematopoietic stem cells (HSCs) that give rise to all types of blood and immune cells. Hematopoietic system comprises surprisingly complex components. While its main priority is to produce red blood cells carrying oxygen throughout the body it ends up being the transportation medium for so much more; in particular the cells of the immune system. 'The HSCs residing deep in the bone marrow are therefore responsible for generating many of the important cell types of the immune system like macrophages, neutrophils as well as lymphoid cells like B and T cells,' explains Yokota. The ability of these stem cells to proliferate into such a variety of essential cell types is both the reason behind their exciting therapeutic potential and the barrier to realising said potential.
'Self-renewal proliferation and multi-lineage differentiation, two seemingly contradictory and incredibly important features of hematopoietic stem cells, are regulated by the changing demand for blood cells in vivo,' outlines Yokota. Because the demand on blood to rapidly address a range of scenarios throughout the body is high it must be able to respond very quickly with the cell types needed. 'For example, if you cut yourself blood responds by creating and bringing to the wound site platelets for clotting, macrophages to kill invading bacteria and multitudes of other cells that regulate inflammation and help fight infections,' he notes. To accomplish this each HSC can differentiate into any type of blood cell; this is the feature of multi-lineage differentiation. 'However, these cells also have the unique self-renewal proliferation feature, meaning when they divide, they can produce one differentiated copy and another stem cell which is able to proliferate indefinitely or differentiate into any other type of blood cell,' Yokota continues. This remarkable flexibility would therefore make them very useful for treating any disorders where any blood cell is lacking, including leukaemia and many symptoms of aging.
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Keywords: ADAPTIVE IMMUNE SYSTEM FUNCTIONING; AGING; B CELLS; EARLY LYMPHOID PROGENITORS; ERYTHROCYTES; ESAM; HAEMATOLOGICAL DISORDERS; HEMATOPOIETIC STEM CELLS; MACROPHAGES; MULTI-LINEAGE DIFFERENTIATION; NEUTROPHILS; REGENERATIVE MEDICINE; SATB1; SELF-RENEWAL PROLIFERATION; T CELLS

Document Type: Research Article

Publication date: March 1, 2019

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