Hematopoiesis Chapter 4 Part 1 PDF

HEMATOPOIESIS CH4 pt1  Hematopoiesis: A quick review Reading: Chapter 4 in textbook Learning objectives: -Get to know what is Hematopoiesis -Understand where, when, & why does it take place -Get acquainted with stem cells especially as they relate to hematopoiesis -Become familiar w...

HEMATOPOIESIS CH4 pt1  Hematopoiesis: A quick review Reading: Chapter 4 in textbook Learning objectives: -Get to know what is Hematopoiesis -Understand where, when, & why does it take place -Get acquainted with stem cells especially as they relate to hematopoiesis -Become familiar with growth factors & interleukins involved in hematopoiesis  Hematopoiesis/ Hemopoiesis What is hematopoiesis? –It is the process of blood cell production, differentiation, and development. Why do we need it? –Cells of the blood are constantly being lost or destroyed. Thus, to maintain homeostasis, the system must have the capacity for self renewal.  Sites of hematopoiesis Developing cells situated outside of BM sinuses  mature cells released into sinus spaces  marrow microcirculation  general circulation.  Yolk Sac: a store of nourishment Early life for the embryo  Later on  Localization of hematopoiesis to bone marrow  The genesis of human hematopoietic stem cells Vincenzo Calvanese,Hanna K. A. Mikkola, The genesis of human hematopoietic stem cells, Blood, 2023, Copyright © 2023 American Society of Hematology  Types of hematopoiesis Medullary hematopoiesis; Hematopoiesis in the bone marrow Extramedullary Hematopoiesis; it occurs in organs other than the bone marrow (liver, spleen, and fetal hematopoietic tissues) – In fetal hematopoietic tissues (liver and spleen) extramedullary hematopoiesis occurs physiologically. – In adults, extramedullary hematopoiesis occurs when the bone marrow cannot meet the needs of the tissues. This can lead to hepatomegaly and/or splenomegaly (increase in size of the liver or spleen because of increased functions in the organs).  Types of Stem Cells Stem cell Description Examples type Gives rise to a whole Cells from early (1-3 Totipotent organism days) embryos Gives rise to the 3 major Some cells of Pluripotent body layers (ecto, meso & blastocyst (5 to 14 endoderm days) Hematopoietic and others: Fetal tissue, cord Multipotent Give rise to a limited number blood, and adult of cell types stem cells Stem cells  Multipotent (hematopoietic) Stem Cells Undifferentiated and uncommitted stem cells residing mostly in the bone marrow Have the ability to self-renew or differentiate into any of the many blood cell types. When stimulated with the proper stimulus, such cells will differentiate into the myeloid lineage or lymphoid lineage. Bone Marrow Stroma Suitable environment for Stem Cell (SC) growth & differentiation. Composed of stromal cells + microvascular network. Stromal Extracellular molecules: cells: Collagen adipocytes Glycoprotein (fibronectin, secrete thrombospondin) Fibroblast Reticulum Glycosaminoglycans cells (hyaluronic acid & Endothelial chondroitin derivates) cells Growth factors; for cell  Hemopoietic Growth Factors (HGF) Glycoprotein hormones; regulate proliferation & differentiation of HPC & function of mature blood cells. Biological effects of HGF mediated through specific receptors on target cells. Activity; – Locally  at the site where they are produced  by cell-cell contact. – Circulate in plasma  HGF May bind to EC matrix  form niches to which SC adhere. Major sources (except erythropoietin): – T-lymphocytes – Monocytes (& macrophages) – Stromal cells Erythropoietin  90% synthesized by peritubular capillary lining cells within the kidney Other erythropoietin is synthesized by hepatocytes Thrombopoietin  largely made in liver  Hematopoiesis microenvironment(s) Growth factors: Functions of GF: Granulocyte-macrophage colony-stimulating factor (GM-CSF) s-like tyrosine kinase 3 (FLt3) receptor  Adhesion Molecules Glycoprotein Mediate the attachment of marrow precursors, leukocytes and platelet to various components of the extracellular matrix: – Endothelium – Other surfaces – Each other