HEMATOPOIESIS

Erwin TaherFK UISU Al-Manar

M E D A N

Introduction

• In the fetus, hematopoiesis takes place initially in the yolk sac and later in the liver and the spleen.

• Islands of hematopoiesis develop in these tissues and then involute as the marrow becomes the primary site for blood cell formation by the seventh month of fetal development.

Tempat Berlangsungnya Haemopoiesis

• Yolk sac

• Liver dan spleen

• Bone marrow

Gambar :Tahapan pembentukan sel darah (hematopoiesis) yang dihubungkan dengan perjalanan umur

The term medullary hematopoiesis refers to the production of blood cells in the bone marrow. extramedullary hematopoiesis indicates blood cell production outside the marrow in the spleen, liver, and other locations.

ORGANIZATION OF HEMATOPOIETIC TISSUES

• The medullary space in which hematopoietic cells develop contains, normally, many adipocytes and a rich vascular supply

• Vascular endothelial cells, marrowfibroblasts, and stromal cells are important sources for the matrix proteins that provide structure to the marrow space and for production of the hematopoietic growth factors that stimulate cell proliferation.

• The vascular endothelial cells also form an important barrier that keeps immature cells in the marrow and permits mature hematopoietic elements to enter the blood.

• The adipocytes may influence hematopoiesis through their effects on the metabolism of androgens and estrogens.

• Marrow macrophages serve to remove effete or apoptotic cells, as well as to clear the blood of foreign materials when it enters the marrow.

• Osteoblasts and osteoclasts maintain and remodel the surrounding cancellous bone and the calcified lattice, which crisscrosses the marrow space.

• The thymus, lymph nodes, mucosa-associated lymphatic tissues (MALT), and the spleen have multiple hematopoietic functions.

-Early in development, they are major sites for hematopoiesis.

-In adulthood, they are principally sites for lymphocyte development, processing of antigens, development of effector T cells, and antibody production

Architecture of Bone Marrow

Hematopoietic Stem Cells

• All cells of the hematopoietic system are derived from common precursor cells, the hematopoietic stem cells.

• These cells are difficult to identify, in part because they normally represent only about 0.05 percent of marrow cells.

Pattern for Development of Blood Cells

BFU-E: burst-forming unit-erythroid; CFU-GM: colony-forming unit-granulocyte-macrophage; CFU-mega: colony-forming unit-megakaryocyte; EPO: erythropoietin; FLT-3L: fms-like tyrosine kinase-3 ligand; G-CSF: granulocyte colony-stimulating factor; GM-CSF: granulocyte-macrophage colony-stimulating factor; IL: interleukin; M-CSF: macrophage colony-stimulating factor; TPO: thrombopoietin; SCF: stem cell factor)

• Many aspects of the earliest steps in this differentiation process are not well understood.

• With lineage commitment, however, differentiation, maturation, and release of cells to the blood come under the control of well-defined hematopoietic growth factors.

• growth factors have overlapping activities for the early phases of differentiation.Later in development, some growth factors are lineage specific, meaning that they govern the maturation and deployment of single lineages. Erythropoietin (EPO), thrombopoietin (TPO), and granulocyte colony-stimulating factor (G-CSF) are the best-characterized lineage-specific factors.

Hematopoietic Growth Factors

• The hematopoietic growth factors, also referred to as hematopoietic cytokines, are a family of glycoproteins produced in the bone marrow by endothelial cells, stromal cells, fibroblasts, macrophages, and lymphocytes and also produced at distant sites from which they are transported to the marrow through the blood.

• Hematopoietic growth factors not only stimulate

cell proliferation but also prolong cell survival; that is, they have antiapoptotic effects.

Factor Other Names Cell Source ChromosomeLocation

Function

EPO Erythropoietin Juxtaglomerular cells 7q Stimulates erythrocyte formation and release from marrow

TPO Thrombopoietin; megakaryocytegrowth and development factor

Hepatocytes, renal andendothelial cells, fibroblasts

3q27 Stimulates megakaryocyteproliferation and plateletformation

G-CSF Granulocyte colony-stimulatingfactor; filgrastim; lenograstim

Endothelial cells, monocytes,fibroblasts

17q11.2-q21 Stimulates formation and functionof neutrophils

GM-CSF Granulocyte-macrophagecolony-stimulating factor

T cells, monocytes, fibroblasts

5q23-q31 Stimulates formation andfunction of neutrophils,monocytes, and eosinophils

M-CSF Macrophage colony-stimulatingfactor; colony stimulatingfactor–1 (CSF-1)

Endothelial cells,macrophages, fibroblasts

5q33.1 Stimulates monocyte formationand function

IL-1a andIL-1b

Interleukin-1a and -1b,endogenous pyrogenhemopoietin-1

Monocytes, keratinocytes,endothelial cells

2q13 Proliferation of T cells, B cells,and other cells; induces feverand catabolism

IL-2 T cell growth factor T cells (CD4+, CD8+), largegranular lymphocytes(natural killer, or NK, cells)

4q T cell proliferation, antitumor andantimicrobial effects

Factor Other Names Cell Source ChromosomeLocation

Function

IL-3 Multi–colony stimulating factor;mast cell growth factor

Activated T cells; large granularlymphocytes (NK cells)

5q23-q31 Proliferation of early hematopoieticcells

IL-4 B cell growth factor; T cellgrowth factor II; mast cellgrowth factor II

T cells 5q23-q31 Proliferation of B cells and T cells;enhances cytotoxic activities

IL-5 Eosinophil differentiation factor;eosinophil colony-stimulatingfactor

T cells 5q23.3-q32 Stimulates eosinophil formation;stimulates T cell and B cellfunctions

IL-6 B cell stimulatory factor II;hepatocyte stimulatory factor

Monocytes, tumor cells, B cellsand T cells, fibroblasts,endothelial cells

7p Stimulates and inhibits cellgrowth; promotes B celldifferentiation

IL-7 Lymphopoietin 1; pre–B cellgrowth factor

Lymphoid tissues and cell lines

8q12-q13 Growth factor for B cells and Tcells

IL-11 Plasmacytoma stimulatingfactor

Fibroblasts, trophoblasts, cancercell lines

19q13.3-q13.4 Stimulates proliferation of earlyhematopoietic cells; inducesacute-phase protein synthesis

Factor Other Names Cell Source ChromosomeLocation

Function

IL-12 Natural killer cell stimulatingfactor

Macrophages, B cells 5q31-q33;3p12-q13.2

Stimulates T cell expansion andinterferon-gamma; synergisticallypromotes early hematopoieticcell proliferation

LIF Leukemia inhibitory factor Monocytes and lymphocytes;stomal cells

22q Stimulates hematopoietic celldifferentiation

SCF Stem cell factor; kit ligand; steelfactor

Endothelial cells; hepatocytes

4q11-q20 Stimulates proliferation of earlyhematopoietic cells and mastcells

FLT-3ligand

fms-like tyrosine kinase 3;STK-1

T cells, stromal cells, andfibroblasts

19q13.3 Stimulates early hematopoietic celldifferentiation; increases blooddendrite cells

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