Hematopoiesis, Differentiation and Maturation of Blood Cells - PowerPoint PPT Presentation

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Hematopoiesis, Differentiation and Maturation of Blood Cells

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Hematopoiesis, Differentiation and Maturation of Blood Cells. Dr.Nadjwa Zamalek Dalimoenthe, SpPK-K Department of Clinical Pathology RSHS/FKUP Bandung – PowerPoint PPT presentation

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Title: Hematopoiesis, Differentiation and Maturation of Blood Cells


1
Hematopoiesis, Differentiation and Maturation of
Blood Cells
  • Dr.Nadjwa Zamalek Dalimoenthe, SpPK-K Department
    of Clinical Pathology RSHS/FKUP Bandung

2
Topics to be discuss
  • Site of hematopoiesis
  • Hematopoietic stem progenitor cells
  • Bone marrow stroma
  • Hematopoietic growth factor
  • Stem cell plasticity
  • Apoptosis
  • Growth factor receptor and signal transduction
  • Adhesion molecules
  • Differentiation of blood cells
  • Maturation of blood cells

3
Reference Books
  1. Essential Hematology. AV Hoffbrand, JE Pettit,
    PAH Moss. 4th ed.
  2. Denise M Harmening. Hematology and Hemostasis.

4
Site of hematopoiesis
AGE SITE
Fetus 0-2 months Yolk sac
2-7 months Liver, spleen
5-9 months Bone marrow
Infants Bone marrow, practically all bones
Adults Vertebrae, ribs, sternum, sacrum and pelvis, proximal ends of femur
  • Developing cells situated outside of BM sinuses
    ? mature cells
  • released into sinus spaces ? marrow
    microcirculation ? general
  • circulation.
  • Hematopoiesis starts with pluripotent stem cell

5
Hematopoietic Stem Progenitor Cells
6
Pluripotent(ial) Hematopoietic Stem Cell
  • Give rise to the separate cell lineage
  • Exact phenotype unkown ? immunological testing
    CD34, CD38-
  • Appearance small/medium size lymphocyte
  • Cell differentiation occurs from the stem cell
    down the erythroid, granulocytic and other
    lineages via the committed hematopoietic
    progenitors cells ? restricted in their
    developmental potential.

7
  • SC has the capability of self-renewal ?
    cellularity remains constant in a normal healthy
    steady state.

8
  • 1 SC capable of producing 106 mature blood
    cells after 20 cell divisions.
  • SC capable of responding to hematopoietic growth
    factors with increased production of one or other
    cell line when the need arises.

9
Bone Marrow Stroma
  • Suitable environment for SC growth dev.
  • Composed of stromal cells microvascular network.
  • Extracellular molecules
  • Collagen
  • Glycoprotein (fibronectin,
  • thrombospondin)
  • Glycosaminoglycans
  • (hyaluronic acid
  • chondroitin derivates)
  • Growth factors ? for cell
  • survival
  • Stromal cells
  • adipocytes
  • Fibroblast
  • Reticulum cella
  • Endothelial cells
  • Macrophages

secrete
10
Hemopoietic Growth Factors
  • Glycoprotein hormones ? regulate proliferation
    differentiation of HPC function of mature blood
    cells.
  • Biological effects of HGF mediated through
    specific receptors on target cells.
  • Act
  • Locally ? at the site where they are produce ? by
    cell-cell contact.
  • Circulate in plasma

11
HGF
  • May bind to EC matrix ? form niches to which SC
    PHC adhere.
  • Major sources (except erythropoietin)
  • T-lymphocytes
  • Monocytes ( macrophages)
  • Stromal cells
  • Erythropoietin ? 90 synthesized in kidney
  • Thrombopoietin ? largely made in liver

12
Leukopoiesis ?also stimulates by endotoxin
13
General Characteristics of Myeloid and Lymphoid
Growth Factors
  • Glycoprotein that act at very low concentration
  • Act hierarchically
  • Usually produced by many cell types
  • Usually affect more than 1 cell lineage
  • Usually active on stem/progenitor cells and on
    functional end cells
  • Usually show synergistic or additive interactions
    with other growth factors
  • Often act on the neoplastic equivalent of a
    normal cell
  • Multiple actions proliferations,
    differentiation, maturation, functional
    activation, prevention of apoptosis.

14
Hematopoietic Growth Factor
Site of action HGF
Stromal cell IL-1, TNF
Pluripotential stem cell Stem cell factor (SCF), Flt ligand (Flt-L)
Multipotential progenitor cell IL-3, GM-CSF, IL-6, G-CSF, thrombopoietin
Committed progenitor cell G-CSF, M-CSF, IL-5 (eosinophil-CSF), erythropoietin, thrombopoietin
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Stem Cell Plasticity
  • Embryonic SC ? totipotent ? generate all tissues.
  • Evidence ? adults SC (in different organs) ?
    pluripotent.
  • Bone marrow
  • Hematopoietic SC
  • Mesenchymal SC ? clinical application ?
    th/mesenchymal disease

17
Apoptosis
  • Homeostasis
  • cell production ? cell destruction
  • Regulated process of physiological cell death ?
    triggered to activate intracellular proteins ?
    lead to cell death.
  • Morphologically
  • Cell shrinkage
  • Condensation of nuclear chromatin
  • Fragmentation of the nucleus
  • Cleavage of intranucleosomal DNA
  • Important proses for maintaining tissue
    homeostasis in hematopoiesis lymphocytes
    development

18
Pathway of apoptosis
19
Growth Factor Receptors Signal Transduction
  • Control hematopoiesis by growth factors
  • Factors acts on cells expressing the
  • corresponding receptors.
  • Binding of GF to its receptor activates
  • by JAKs ? then phosphorylate STATs
  • which translocate to the nucleus and
  • activate transcription of specific
  • genes

20
Adhesion Molecules
  • Glycoprotein
  • Mediate the attachment of marrow precursors,
    leukocytes and platelet to various components of
    the extracellular matrix to
  • Endothelium
  • Other surfaces
  • Each other
  • On leukocyte ? receptors ? interact with ligand
  • 3 main families Immunoglobulin, selectins,
    integrin

21
Any questions?
22
Blood Cell Proliferation, Differentiation and
Maturation
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Normal and Abnormal Maturation of Blood Cells
26
Normal Cell Maturation
  • Changes in cytoplasm
  • Changes in nucleus
  • Reduction in cell size
  • Gradual transformation
  • Changes are simultaneous and paralel

27
Erythropoiesis
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Changes in Cytoplasma
  • Loss of basophilia
  • Romanowsky staining (Giemsa)
  • The more basophilic cytoplasma, the more immature
    cell
  • Cytoplasmic granules in granulocytes
  • Azurophil (primary granules)
  • Specific (secondary granules)
  • Eosinophilic
  • Basophilic
  • Neutrophilic

31
Changes in Cytoplasma
  • Elaboration of hemoglobin blue cytoplasm in
    pronormoblast and red cytoplasm in erythrocyte in
    pronormoblast

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Changes in Nucleus
  • Nuclear Maturation
  • Shape
  • Round or oval in blasts
  • Striking changes in granulocytes
  • Structure delicate netlike or sponge like
  • chromatin in blasts
  • Chromatin strands become more coarse and clumped
    as the cells matures
  • Reduction in the number of nucleoli

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Reduction in Cell Size
  • A feature of all cells, except in the
    megakaryocytic series.
  • N/C ratio is high in young cells
  • and low in mature cells.

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Abnormal Cell Maturation
  • Asynchronous maturation of cytoplasma
  • and nucleus ? atypical cells.
  • Granulocytes
  • - agranular
  • - persistent primary granules
  • - abnormal inclusions
  • - Large nucleus
  • - Hypersegmentation/hyposegmentation
  • Erythrocytes
  • persistent basophilia

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Thank You Very Much
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