HEMATOPOIESIS

Erwin Taher FK UISU Al-Manar MEDAN

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 unitmegakaryocyte; EPO: erythropoietin; FLT-3L: fms-like tyrosine kinase-3 ligand; G-CSF: granulocyte colony-stimulating factor; GMCSF: 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

Chromosome Location
7q

Function

EPO

Erythropoietin

Juxtaglomerular cells

Stimulates erythrocyte formation and release from marrow Stimulates megakaryocyte proliferation and platelet formation Stimulates formation and function of neutrophils Stimulates formation and function of neutrophils, monocytes, and eosinophils

TPO

Thrombopoietin; megakaryocyte growth and development factor

Hepatocytes, renal and endothelial cells, fibroblasts Endothelial cells, monocytes, fibroblasts T cells, monocytes, fibroblasts

3q27

G-CSF

Granulocyte colony-stimulating factor; filgrastim; lenograstim Granulocyte-macrophage colony-stimulating factor

17q11.2-q21

GM-CSF

5q23-q31

M-CSF

Macrophage colony-stimulating factor; colony stimulating factor1 (CSF-1)

Interleukin-1a and -1b, endogenous pyrogen hemopoietin-1 T cell growth factor

Endothelial cells, macrophages, fibroblasts

5q33.1

Stimulates monocyte formation and function

Proliferation of T cells, B cells, and other cells; induces fever and catabolism T cell proliferation, antitumor and antimicrobial effects

IL-1a and IL-1b

Monocytes, keratinocytes, endothelial cells T cells (CD4+, CD8+), large granular lymphocytes (natural killer, or NK, cells)

2q13

IL-2

4q

Factor

Other Names

Cell Source

Chromosome Location
5q23-q31

Function

IL-3

Multicolony stimulating factor; mast cell growth factor

Activated T cells; large granular lymphocytes (NK cells)

T cells

Proliferation of early hematopoietic cells

Proliferation of B cells and T cells; enhances cytotoxic activities Stimulates eosinophil formation; stimulates T cell and B cell functions Stimulates and inhibits cell growth; promotes B cell differentiation

IL-4

B cell growth factor; T cell growth factor II; mast cell growth factor II Eosinophil differentiation factor; eosinophil colony-stimulating factor B cell stimulatory factor II; hepatocyte stimulatory factor

5q23-q31

IL-5

T cells

5q23.3-q32

IL-6

Monocytes, tumor cells, B cells and T cells, fibroblasts, endothelial cells Lymphoid tissues and cell lines Fibroblasts, trophoblasts, cancer cell lines

7p

IL-7

Lymphopoietin 1; preB cell growth factor Plasmacytoma stimulating factor

8q12-q13

Growth factor for B cells and T cells Stimulates proliferation of early hematopoietic cells; induces acute-phase protein synthesis

IL-11

19q13.3-q13.4

Factor

Other Names

Cell Source

Chromosome Location
5q31-q33; 3p12-q13.2

Function

IL-12

Natural killer cell stimulating factor

Macrophages, B cells

Stimulates T cell expansion and interferon-gamma; synergistically promotes early hematopoietic cell proliferation Stimulates hematopoietic cell differentiation

LIF

Leukemia inhibitory factor

Monocytes and lymphocytes; stomal cells Endothelial cells; hepatocytes

22q

SCF

Stem cell factor; kit ligand; steel factor

4q11-q20

Stimulates proliferation of early hematopoietic cells and mast cells Stimulates early hematopoietic cell differentiation; increases blood dendrite cells

FLT-3 ligand

fms-like tyrosine kinase 3; STK-1

T cells, stromal cells, and fibroblasts

19q13.3