Physiology of Hematopoiesis

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: James Nasr[2]

Physiology

• The circulating blood cells are produced in bone marrow after a series of events termed as hematopoiesis.
• The bone marrow has an tremendous regenerative ability; it is estimated that 10 trillion red blood cells and 80 to 90 trillion leukocytes are formed per hour at the basal rate.
• In addition to that, while cell numbers are maintained within narrow limits in normal subjects, they can be promptly increased when required.
• Bone marrow primarily has small percentage of pleuripotent stem cells which give rise to various progenitor cells.
• Hematopoeisis occurs in the vertebrae, pelvic bones, metaphysis of long bones such as femur, humerus in basal state.
• However, during certain stressful conditions that require rapid and massive hematopoiesis such as thalassemia it then returns to its former site, liver, spleen and sometimes lymph nodes.
• These hematopoietic stem cells (HSCs are multipotent and have the ability to differentiate into the cells of all 10 blood lineages:
  • Erythrocytes
  • Platelets
  • Neutrophils
  • Eosinophils
  • Basophils
  • Monocytes
  • T and B lymphocytes
  • Natural killer cells
  • Dendritic cells
• This differentiation is mediated through multiple growth factors and cytokines.  
• The hematopoietic stem cells (HSCs) and progenitor cells are supported by a stromal cell network that provides cell-cell contact support.
• The stromal network provides two major functions:
• An adhesive framework onto which the developing cells are bound, these cells produce:
  • A variety of adhesion molecules.
  • Hematopoietic Growth factors or cytokines that are thought to support the survival, proliferation, and differentiation of HSCs and progenitors.
• Primitive mesenchymal stromal cells (MSCs) are thought to have the capacity to differentiate into following:
  • Osteolineage cells
  • Chondrocytes
  • Adipocytes
  • Perivascular cells
• Overall Differentiation of myeloid progenitors is mediated through:
  • The production of essential  hematopoietic growth factors.
  • Several signaling pathways have come up as integral control devices of HSC fate, such as:
    • Notch
    • Wingless-type (Wnt)
    • Sonic hedgehog (Shh)
    • Smad pathways
• These signaling circuits provide an important structure for our understanding of HSC regulation, alongwith providing information of how the bone marrow micro environment couples and integrates extrinsic with intrinsic factors responsible for HSC differentiation and development of chronic myeloid leukemia.