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Hematopoiesis

Hematopoiesis

UKRAINIAN MEDICAL STOMATOLOGICAL ACADEMY Department of , Cytology and Embryology

Hematopoiesis

PhD, Teacher of Department of Histology, Cytology and Embryology Skotarenko Tetiana Plan of lecture

 1. General characteristics of the organs of hematopoiesis.  2. Embryonic hematopoiesis.  3. Postembryonic hematopoiesis.  4. The modern theory of hematopoiesis.  5. Stem cells.  6. Characterization of cells of all classes of hematopoiesis.

2 Hematopoiesis is development of the cells.

Mature blood cells have a relatively short life span, and the population must be replaced by the progeny of stem cells produced in the hematopoietic organs. Types of hematopoiesis ► embryonic (prenatal) hematopoiesis which occurs in embryonic life and results in development of a blood as tissue, ► postembryonic (postnatal) hematopoiesis which represents process of physiological regeneration of a blood. Development of erythrocytes name an , of – , of thrombocytes - thrombopoiesis, of - monopoiesis, of lymphocytes and immunocytes - lympho- and immunopoiesis. ► In the prenatal period the hematopoiesis serially occurs in several developing organs. ► After birth the hematopoiesis occurs in the of a skull, ribs, sternum, pelvic bones, epiphysises of the lengthy bones. Prenatal hematopoiesis 1. The primary (megaloblastic) stage.

During 2-3 weeks of development in the wall of the yolk sac the clumps of mesenchymal cells - blood islands - are formed. Prenatal hematopoiesis 1. The primary (megaloblastic) stage Cells on periphery of each island form the endothelium of primary blood vessels. The cells of the central part of an island form the first blood cells - primary erythroblasts - the large cells containing a nucleus and embryonic Hb. Prenatal hematopoiesis 1. The primary (megaloblastic) stage

► Leucocytes and thrombocytes at this stage are not present. ► On 12-th week the hematopoiesis in a yolk sac comes to an end. Prenatal hematopoiesis 2. Hepatic phase

In a liver the hematopoiesis begins on 5-6 week of development. Granulocytes, thrombocytes and erythroblasts, and erythrocytes (denuclearized cells) are formed here. By the end of 5-th month intensity of a hematopoiesis in the liver decreases. Prenatal hematopoiesis 3. Splenic phase The hematopoiesis in the lien is most expressed with 4 for 8 month of prenatal development. Here erythrocytes and a small amount of granulocytes and thrombocytes are formed. Directly before of a birth the main function of the lien the formation of lymphocytes become. Prenatal hematopoiesis 4. Hematopoiesis in the thymus On 7-8 week of development in thymus T-lymphocytes are formed.

5. Hematopoiesis in the lymph nodes On 9-10 week of development lymph nodes can produce erythrocytes, granulocytes and . Prenatal hematopoiesis 6. The bone marrow hematopoiesis (myeloid stage) Within 5-th month of development a hematopoiesis begins in the bone marrow where all types of blood cells are formed. By the moment of a birth, after a birth and at the adult the hematopoiesis is limited to the bone marrow and the lymphoid tissue. Prenatal hematopoiesis 6. The bone marrow hematopoiesis (myeloid phase)

When the bone marrow is not capable satisfy the increased inquiry about formation of blood cells, hematopoietic activity of a liver, lien and lymph nodes can be reduced. Postembryonic (postnatal) hematopoiesis

process of physiological

regeneration of blood

15 16 Postnatal hematopoiesis

In the postnatal period the hematopoiesis is carried out in the special hematopoietic tissues: myeloid and lymphoid. The

is functionally leading tissue of the red bone marrow, which is found in the medullary canals of long bones and in the cavities of cancellous bones. The myeloid tissue contains stem cells and is a place of formation of erythrocytes, granulocytes, monocytes, thrombocytes, precursors of lymphocytes. The lymphoid tissue is found in lymphoid organs - a thymus, a spleen, lymph nodes, tonsils, Peyers’s patches, vermiform appendix and the numerous lymphoid formations available in a wall of organs of various systems. In it there is formation of Т-and B-lymphocytes. The general laws of development of formed elements of the blood

Now it is proved, that as the common source of development of all formed elements of the blood is pluripotential . This position for the first time is formulated by professor A.A.Maksimov in the beginning of XX century in the unitary (monophyletic) theory of the hematopoiesis. Classes of the cells in the histogenetic rows of hematopoiesis

I - pluripotential stem cell; II - multipotential stem cells; III - uni- or bipotential progenitor cells; IV - precursor cells (blasts), V – maturing cells, VI – mature cells 22 Stem cells

► can produce all blood cell types, because these cells are called pluripotential. Stem cells look like small lymphocytes. ► are concentrated at the adults mainly in the red bone marrow, however are found out in the blood, circulating in which they get in other organs of a hematopoiesis. The basic properties of stem cells:

► 1. Have ability to self-renewing; ► 2. Rarely divide; ► 3. Are capable to form all kinds of formed elements of the blood; ► 4. Are stable against action of damaging factors; ► 5. Found in the places well environment proofed (alveoli in a bone tissue) and having an abundant blood supply; ► 6. Circulate in a blood, migrating in other organs of a hematopoiesis. Multipotential stem cell proliferates and forms ► one cell lineage that will become lymphocytes (lymphoid cells), and ► another lineage that will form the myeloid cells that develop in bone marrow (granulocytes, monocytes, erythrocytes, and megakaryocytes).

Both these types of stem cells are called multipotential stem cells. Multipotential stem cells

have low mitotic activity, self-renewing, found in the red bone marrow. Progenitor cells The proliferating multipotential stem cells form daughter cells with reduced potentiality: uni- or bipotential progenitor cells.

Progenitor cells have high mitotic activity, self-renewing, common in marrow and lymphoid organs. Cells forming colonies of specific cell types are called colony-forming cells (CFC), or colony-forming units (CFU). The convention in naming these various cell colonies is to use the initial letter of the cell each colony produces. Thus, MCFC denotes a - colony-forming cell, ECFC produces , and MGCFC produces monocytes and granulocytes, and so on. Precursor cells (blasts) ► Uni- or bipotential progenitor cells generate precursor cells (blasts). ► Precursor cells have high mitotic activity, not self-renewing, common in marrow and lymphoid organs, unipotential. Each precursor cell forms of a concrete kind of cells.

The maturing of each kind of cells passes series of stages which form compartment of maturing cells. Mature cells represent last compartment. Growth factors (hematopoietins)

The differentiation of pluripotential cell in unipotential is determined by action of some specific factors – growth factors: erythropoietins (for erythroblasts), granulopoietins (for ), lymphopoietins (for lymphoblasts), megakaryopoietins (for ), etc. Hematopoietic growth factors

are produced by stromal components of hematopoietic tissues and organs, and first of all, reticular . They are produced also by epithelial cells of a thymus, cells of an endothelium, and also the cells which were outside of hematopoietic tissues (for example, erythropoietin is produced by the cells of liver and kidney). Erythropoiesis is process of formation and a maturing of the erythrocytes. Erythron is erythroidal differon, representing set of the cells - from stem cells up to mature erythrocytes. BFU - burst forming unit - is named so on the ability to form quickly colony of erythroidal cells of some hundreds elements. Process of development of erythrocytes is described by sequence:

Pluripotential stem cell – myeloid multipotential cell – erythrocyte- burst forming unit (EBFU) – erythrocyte-colony forming unit (ECFU) – – basophilic erythroblast- polychromatophilic erythroblast – orthochromatophilic erythroblast – – Erythrocyte. Process of a differentiation of precursors of erythrocytes in mature formed elements includes: 1) decrease of the cell sizes; 2) progressive decrease of polyribosomes (basophilia) and all organelles; 3) progressive increase and accumulation of in cytoplasm (acidophilia); 4) decrease and further loss of ability to division; 5) condensation of a nucleus and its subsequent removal from the cell. Erythropoiesis

37 Erythropoiesis The first recognizable cell in the erythron is the proerythroblast. It is a large cell with basophilic cytoplasm. The next stage is represented by the basophilic erythroblast (early normoblast) with a strongly basophilic cytoplasm and a condensed nucleus. Basophilia of these two cell types is caused by the large number of polyribosomes involved in the synthesis of hemoglobin. Erythropoiesis During the next stage, polyribosomes decrease and the cytoplasm begin to be filled with hemoglobin. Staining at this stage causes several colours to appear in the cell— the polychromatophilic erythroblast (intermediate normoblast). Erythropoiesis Progressive increase in the cytoplasmic hemoglobin content results in uniformly acidophilic cytoplasm – the orthochromatophilic erythroblast (late normoblast). At a given moment this cell puts forth a series of cytoplasmic protrusions and expels its nucleus. Erythropoiesis The reticulocyte loses nucleus, polyribosomes and becomes a mature erythrocyte. The process of erythropoiesis takes about 1 week. The rate of erythropoiesis is controlled by the erythropoietin secreted by the kidneys. Erythropoiesis

The erythroblastic island consists of surrounded by erythrocyte progenitor cells. Erythropoiesis The plasma membranes of the macrophages exhibit long cytoplasmic processes and deep invaginations which accommodate the dividing erythroid cells. As the erythroid cell differentiates, it migrates outwards along the cytoplasmic process of the macrophage. Granulopoiesis

is formation and a differentiation of granulocytes, occurs in the red bone marrow. Granulopoiesis Process of development of granulocytes is described by sequence: а) neutrophilic: Pluripotential stem cell – myeloid multipotential cell – bipotential monocyte- -colony-forming cell (MGCFC) – granulocyte-colony-forming cell (GCFC); b) basophilic: Pluripotential stem cell – myeloid multipotential cell – -colony-forming cell (BCFC); c) eosinophilic: Pluripotential stem cell – myeloid multipotential cell –-colony-forming cell (ECFC); Granulopoiesis The subsequent stages of development of granulocytes precede for all three types of cells the same: – – – – – segmented granulocyte. Granulopoiesis

I – myelocyte; II – meta- myelocyte; III – band cell; IV – mature neutrophil Process of the differentiation of precursors of granulocytes in mature cells includes: ● 1) Decrease of the cell sizes; ● 2) Decrease and further loss of ability to division; ● 3) Change of the form of a nucleus - from spherical and kidney-shaped to and S- or horseshoe-shaped, its segmentation; ● 4) Development and accumulation of granules in cytoplasm; ● 5) Increase of mobility of a cell. is formation and a differentiation of monocytes - occurs in the red bone marrow. Process of development of monocytes is described by sequence: Pluripotential stem cell – myeloid multipotential cell – bipotential monocyte-granulocyte-colony-forming cell (MGCFC) – monocyte-colony- forming cell (GCFC) – - – monocyte. Process of transformation of in monocytes includes: ● 1) The further increase in the sizes of a cell mainly due to increase of volume of cytoplasm; ● 2) Decrease of basophilia of cytoplasm; ● 3) Accumulation in cytoplasm of azurophilic granules; ● 4) Change of the form of a nucleus which becomes kidney-shaped. Lymphocytopoiesis is formation and differentiation of lymphocytes in the red bone marrow and lymphoid organs. Process of development of lymphocytes is described by sequence: Pluripotential stem cell – lymphoid multipotential cell ––lymphocyte- colony-forming cell (LCFC) – lymphoblast – B- and T-lymphocytes. Thrombocytopoiesis is formation of in the red bone marrow by fragmentation of the cytoplasm of mature megakaryocytes. Process of development of thrombocytes is described by sequence: Pluripotential stem cell – myeloid multipotential cell –– - colony-forming cell – - megakaryocyte – platelets. Megakaryocyte is a (35-150 μm in diameter) with an irregularly lobulated nucleus. The cytoplasm contains numerous mitochondria, a well- developed rough endoplasmic reticulum, and an extensive Golgi complex. Megakaryocyte With maturation of the megakaryocyte, numerous invaginations of the plasma membrane ramify throughout the cytoplasm, forming the demarcation membranes. Platelets are formed by fragmentation of the megakaryocyte cytoplasm. Discussion questions

 In myeloid tissue punctate child 6 years cells are found. In these cells there were remove the nucleus during the process of differentiation. What kind of hematopoiesis, characterized by morphological changes in the data.

 In punctate of red bone marrow ther were found a significant decrease in the number of megakaryocytes. What changes in peripheral blood is accompanied?

 During postembryonal haemopoiesis in the red bone marrow the cells of one of the cellular differons demonstrate a gradual decrease in cytoplasmic basophilia as well as an increase in oxyphilia, the nucleus is being forced out. Such morphological changes are typical for the following haemopoiesis type:

56 Literature list

 Gartner L.P., Hiatt J.L.: Color Atlas and Text of Histology. 6th edition. Wolters Kluwer, 2014.  Ross M., Pawlina W.: Histology: a Text and Atlaswith Correlated Cell and Molecular Biology. 8th edition. Wolters Kluwer, 2018.  Young B., Woodford P., O´Dowd G.: Wheater´s Functional Histology. A text and colour atlas. 6th edition, Churchill Livingstone, 2013.  Sadler T.: Langman´s Medical Embryology, 13thedition, Wolters Kluwer 2014  Moore K.L., Persaud T.V.N., Torchia M.G.: Before We Are Born, 9th Edition. Elsevier, Philadelphia, 2016.  Moore K.L., Persaud T.V.N., Torchia M.G.: The Developing Human, 10th Edition. Clinically Oriented Embryology. Elsevier, Philadelphia, 2016.C  Carlson B.M.:Human Embryology and Developmental Biology, 5th edition, Saunders Elsevier 2013

57  Barbara Young.: Wheater's Functional Histology, A Text and Colour Atlas: 6th edition, Elsevier Health Sciences, 2013  Mescher.: Junqueira's Basic Histology, Text and Atlas, Fourteenth Edition, McGraw-Hill Education – Europe, 2015  James Lowe.: Stevens & Lowe's Human Histology, 4th Edition, Elsevier Health Sciences, 2014  Dongmei CuiJohn P. NaftelJonathan D. FratkinWilliam DaleyJames C. Lynch.: Atlas of Histology, With Functional and Clinical Correlations, Lippincott Williams and Wilkins, 2010  Pawlina & Ross.: Histology: A Text and Atlas, With Correlated Cell and Molecular Biology, Lippincott Williams and Wilkins, 2015.

58 Contact

 Skotarenko Tetiana

 PhD, Teacher Department of Histology, Cytology and Embryology

[email protected]  0956097220

59 Thank you for attention

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