Monophyletic theory of hematopoiesis. Stem cellsTERESHCHENKO IRYNA

SECOND MEDICAL FACULTY, CHARLES UNIVERSITY IN PRAGUE

Theories of Blood Cell Formation

Monophyletic theory Dualistic theory

Polyphyletic theory

Also known as Unitary Theory, first introduced by russian histologist A.A.Maksimov more than 100 years ago, suggest that there is a common parent cell of all forming elements of blood – indifferent mesenchymal cell, which is able to form cells of lymphoid, myeloid and erythroblast line.

Dualistic theory includes two sources of hematopoiesis: myeloid and lymphoid.

Proposed by: Erlich,Schridde, O. Naegeli

Also known as Trialistic theory, suggest different groups of blood cells originate from different stem cells. Three systems: myeloid, lymphoid and reticuloendothelial.

Proposed by: L. Aschoff

Exist three theories of hematopoiesis (Blood Cell Formation), but the most common still is Unitary (Monophyletic theory).

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“All blood elements develop from one origin cell – stem cell Monophyletic theory, A. A. Maksimov

The term "stem cell” Maksimov proposed in 1908.

Stem Cell

Stem Cells - a cell that has the ability to continuously divide and differentiate (develop) into various other kind(s) of cells/tissues.

has the ability to self-support of its number;

rarely divided; new formed elements are formed by dividing progenitors;

is a source of all kinds of blood cells (stem cell is pluripotent – has an ability to develop into all kinds of cells of tissue);

from all the cells, stem cell is most resistant to damage.

Classification

Totipotent stem cells are found only in early embryos. Each cell can form a complete organism.

Pluripotent stem cells Obtained from the inner cell mass of the blastocyst, able to differentiate into almost all cells of the three germ layers – but not into an embryo.

Multipotent stem cells Found in most tissues, can produce a limited range of differentiated cell lineages appropriate to their location (e.g., Hematopoietic stem cells from the bone marrow). Limited in what the cells can become.

Unipotent cells capable of generating only one cell type (epidermal stem cells, adult liver stem cells).

Stem cells can be classified into four broad categories, based on their ability to differentiate:

Stem Cells

Hemopoiesis (Hematopoiesis)

Haematopoiesis is a process of formation of blood cellular components. All cellular blood components are derived from haematopoietic stem cells (HSC).

Sources of hematopoietic stem cells in human Umbilical Cord blood.

Peripheral blood.

Bone marrow

Hemapoiesis (Hematopoiesis)

Hemo = Hemato = Blood

Poiesis = Production

Hemopoiesis system Bone marrow Spleen Liver Thymus Lymph node

Stages of Hemopoiesis

Include: Proliferation (reproduction by neoplasms);

Differentiation (sequential process of mitosis during which cells acquire specific morpho-functional traits)

Maturation of cells (process when the cell continues to evolve but no longer divided)

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STEM CELLS THAT GIVES RISE TO ALL BLOOD CELLS TYPES IS INCLUDING: 1. LYMPHOID STEM CELL (Progenitor):

T- Cell

B- Cell

Natural Killer (NK-Cell)

- IS THE TYPE OF CYTOXIC LYMPHOCYTES.

2. MYELOID STEM CELL (Progenitor):

Monocytes Neutrophils Basophils Eosinophils Erythrocytes Megakaryocytes - Platelets

Immature vs Mature cells

The immature blast cell: Large cell, high Nucleo-

cytoplasmic ratio

Large nucleus, fine chromatin

& nucleoli

Small amount of dark blue

cytoplasm

With maturation: Cells become smaller

Nuclear chromatin clumps,

nucleoli disappear

Hgb or granules appear

N:C ratio decreases

During maturation cells changing its properties.

Development of erythrocyteDuring development erythrocyte loses its nucleus.

Phase 1: Ribosome synthesis

Phase 2:Hgb accumulation

Phase 3:Ejection of nucleus

Development pathway

Hemopoietic growth factors

Erythropoietin (EPO)

produces primarily by cells in the kidney that lie between the kidney tubules (peritubular interstitial cells)

Control erythropoiesis - red blood cell production

Required for a myeloid progenitor cell to become erythrocyte

Thrombopoietin ( TPO)

Hormone produced by by the liver

Stimulates the formation of platelets from megakaryocytes (megakaryocytopoiesis)

A hormone-like substances (protein) that stimulate bone marrow to produce blood cell and promote the proliferation of blood cells.

Classes of stem cells

By degree of maturity the cells are divided into 6 classes: 1 class – Stem cells (Pluripotent)

2 class – half-stem cells (Polipotent)

3 class – Unipotent cells (give rise to only one type formed elements)

4 class – Blasts (large cells)

5 class - Differentiating precursors

6 class - Mature formed elements circulating in the bloodstream

Bone marrow smear shows developing cells differing in sizes, nuclear shapes, contour and chromatin pattern, cytoplasm for basophilia and presence or absence of granules. Wrights – Giemsa x 200

Human bone marrow:Neutrophilic myelocyte (h), metamyelocyte (a), and mature (e) and band (g) neutrophil. W-G x 400.

A myelocyte is a young cell of the granulocytic series, occurring normally in bone marrow, but not circulating in blood (except when caused by some disease). Develop into neutrophil. Neutrophils are normally found in the bloodstream. During the beginning (acute) phase of inflammation, particularly as a result of bacterial infection, environmental exposure, and some cancers, neutrophils are one of the first-responders of inflammatory cells to migrate towards the site of inflammation.

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Human bone marrow: Very early neutrophilic promyelocyte (a) is very basophilic & chromatophilic, proerythroblast (c). Wrights-Giemsa x 400

Promyelocyte (or progranulocyte) is a granulocyte precursor, developing from the myeloblast and developing into the myelocyte. In the end of the 4th phase develop into Basophil.

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Human bone marrow: Neutrophilic metamyelocytes (f, g), mature eosinophil (h), neutrophlic myelocyte (i), eosionophilic myelocyte (j), lymphocyte (k). W-Giemsa x 400

A metamyelocyte is a cell undergoing granulopoiesis, derived from a myelocyte, and leading to a band cell. Develop into eosinophil, neutrophil or basophil.

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Eosinophils are white blood cells and one of the immune system components responsible for combating multicellular parasites and certain infections in vertebrates.

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Lymphocytes are cellular components of the adaptive immune response.

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Human bone marrow: Band neutrophil (b), neutrophilic metamyelocytes (e), late neutrophilic myelocyte (d), normoblast (f). Wrights-Giemsa x 400.

A metamyelocyte is a cell undergoing granulopoiesis, derived from a myelocyte, and leading to a band cell. Develop into eosinophil, basophil or neutrophil.

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Human bone marrow: Normoblasts (b, d, f) differing in sizes and degree of chromatin clumping, late erythroblasts ( c). W-G x 400.

Normoblast (erythroblast) is a type of red blood cell which still retains a cell nucleus. It is the immediate precursor of a normal erythrocyte.Develop into erythrocyte.

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Human bone marrow: A megakaryocyte shedding its cytoplasm to form platelets (arrow). W-G x 400.

Megakaryocytes belong to myeloid progenitor. Produced primarily by the liver, kidney, spleen, and bone marrow.Develop into thrombocytes.

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Clinical Application1. Cells, created by hemopoiesis

2. Stem cells

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Indicators of red blood includes:

Hgb – hemoconcentration

Hgb– anemia

MCV is increased, the cell is known as a macrocyte and when it is decreased - microcyte.

MCV – megoblastic anemia

MCV – microcytic anemia

Color index (CI) - ratio between the percentage of Hgb and the percentage of red blood cells in the blood. It is useful in determining the type of anemia. It is raised in pernicious anemia and megaloblastic anemia. It is reduced in iron deficiency anemia.

Hgb is in erythrocytes so it is important that the amount of Hgb was enough, because it carries the transfer function of O2 to the cells of various organs.

Hgb

Erythrocytes

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Indicators of red blood includes:

L – Leukocytosis (exist an infection in the body, which has launched production of white blood cells)

L – Leukopenia

Neutrophils - leukocytic formula (wbc)

N – eosinophilia (marker of allergies and parasitic diseases)

Leukocytes (granulocytes) - white blood cells that are involved in the protection (bacterial etc).

All this indicates the acute inflammation process in the body.

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Stem cells

Used in case when the base of the disease is a Chronic Inflammation (Chronic neuroinfections): Poliomyelitis; Cerebral Palsy; Blood diseases; Genetic disorders; Used for reprogramming damaged (disturbed) hemopoiesis by disease.

Stem Cells Banks

Public (donors) which shall be the umbilical cord / placental blood for public use -their work is funded by the state;

Private storage, in which stem cells are the property of one man and may be used only for him (he accordingly assume all costs associated with preparation and storage).

Nowadays, there are two types of banks of stem cells fromumbilical/placental blood: