UKRAINIAN MEDICAL STOMATOLOGICAL ACADEMY Department of Histology, 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 blood 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 erythropoiesis, of granulocytes – granulopoiesis, of thrombocytes - thrombopoiesis, of monocytes - 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 bone marrow 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 megakaryocytes . 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 myeloid tissue 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 stem cell. 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 monocyte- colony-forming cell, ECFC produces eosinophils, 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 myeloblasts), lymphopoietins (for lymphoblasts), megakaryopoietins (for megakaryoblasts), etc. Hematopoietic growth factors are produced by stromal components of hematopoietic tissues and organs, and first of all, reticular macrophages. 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) – proerythroblast – basophilic erythroblast- polychromatophilic erythroblast – orthochromatophilic erythroblast – reticulocyte – 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 hemoglobin 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