HEMATOPOIETIC STEM CELLS

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Introduction:

Hematopoietic stem cells (HSCs) are the stem cells that give rise to other blood cells. This process is called haematopoiesis. In vertebrates, the very first definitive HSCs arise from the ventral endothelial wall of the embryonic aorta within the (midgestational) aorta-gonad-mesonephros region, through a process known as endothelial-to-hematopoietic transition. In adults, haematopoiesis occurs in the red bone marrow, in the core of most bones. The red bone marrow is derived from the layer of the embryo called the mesoderm.

Haematopoiesis is the process by which all mature blood cells are produced. It must balance enormous production needs (the average person produces more than 500 billion blood cells every day) with the need to regulate the number of each blood cell type in the circulation. In vertebrates, the vast majority of haematopoiesis occurs in the bone marrow and is derived from a limited number of hematopoietic stem cells that are multi-potent and capable of extensive self-renewal.

Hematopoietic stem cells give rise to different types of blood cells, in lines called myeloid and lymphoid. Myeloid and lymphoid lineages both are involved in dendritic cell formation. Myeloid cells include monocytes, macrophages, neutrophils, basophils, eosinophils, erythrocytes, and megakaryocytes to platelets. Lymphoid cells include T cells, B cells, natural killer cells, and innate lymphoid cells. The definition of hematopoietic stem cell has developed since HSCs were first discovered in 1961. The hematopoietic tissue contains cells with long-term and short-term regeneration capacities and committed multi-potent, oligo-potent, and uni-potent progenitors. Hematopoietic stem cells constitute 1:10,000 of cells in myeloid tissue. HSC transplants are used in the treatment of cancers and other immune system disorders.

Mechanism:

Hematopoietic stem cells (HSC) are characterized by their extensive self-renewal capacity and pluripotency. The probabilities of asymmetric versus symmetric division of HSC can be stochastically determined or influenced by external signals. There are many in vitro systems involving either bone marrow stromal support or provision of a combination of recombinant hematopoietic growth factors or both that can maintain HSC proliferation and differentiation over many weeks. However, the goal of significant expansion of the HSC population in vitro has proved more elusive. There has been an explosive increase in knowledge of the cellular and molecular bases of HSC regulation with the identification of pathways implicating Notch, Wnt, and Hedgehog as well as the cytokine signalling through the cKit, Flt3, IL-6-R, mpl, and Tie-2 receptors and downstream pathways involving Jak/STAT and homolog proteins. There is considerable redundancy in pathways regulating HSC, and both additive and synergistic interactions between different pathways determine the balance between self-renewal and differentiation. With the identification of specific niches within the bone marrow, including endosteal and endothelial, it is now recognized that intimate interactions between HSC and regulatory components of the marrow microenvironment (osteoblasts, osteoclasts, granulocytes, mesenchyme cells, endothelium) determine HSC proliferative status, pool size, differentiation, and mobilization. The migration of HSC between different niches and the vascular compartment is regulated by the chemotactic action of stromal-derived chemokine SDF-1 acting through its receptor CXCR4, in combination with CD44 and hyaluronic acid. The release of various proteases within the marrow environment leads to cleavage of stromal and HSC-associated adhesion molecules, receptors, cytokines, and chemokine, providing a further level of regulation.

Insights in stem cells is an international open access, peer-reviewed academic journal. The journal is dedicated to publish quality articles with an emphasis on basic, translational and clinical research on stem cell. Insights in stem cell  publishes articles that cover all aspects of Stem cell therapy, Stem cell transplant, Stem cell biology, Cancer stem cell, Therapeutic cloning, Neural stem cells, Somatic stem cell, regenerative medicine.

Submissions online at: https://www.imedpub.com/submissions/insights-stem-cells.html

Regards,                                                                         

Alina Grace,

Associate Managing Editor,

Insights in Stem Cells