Transcript STEM CELLS
Hemopoiesis Lec.2 Lifespan and production of blood cells Cell type Red Cells Neutrophils Platelets Lymphocytes Approximate lifespan Production rate cells/day Production rate cells/sec Production rate Kg/year 120 days 2 x 1011 2.3 million 7.3 t½ 6 hours 3 x 1010 350,000 10.9 7 days 1 x 1011 1.2 million 4.6 t½ 10 days 1 x 1010 116,000 3.7 Annual total 26.5 Kg So our body is in a continuous dynamic and a very rapid cell turnover to be able to live. HOW ? It’s the Stem Cell ! HEMOPOIESIS: INTRO Hemo: Referring to blood cells Poiesis: “The development or production of” The word Hemopoiesis refers to the production & development of all the blood cells: Erythrocytes: Erythropoiesis Leucocytes: Leucopoiesis Thrombocytes: Thrombopoiesis. HEMOPOIESIS Hemopoiesis depends on 3 important components: the bone marrow stroma (Local control) the hemopoietic stem and progenitor cells the hemopoietic growth factors (Humoral control) Interaction of stromal cells, growth factors and haemopoietic cells Stromal Cells of BM Endothelial cells Fat cells Fibroblasts Lymphocytes Macrophage STEM CELL THEORY The dazzling array of all the blood cells are produced by the bone marrow. They all come from a single class of primitive mother cells called as: PLURIPOTENT STEM CELLS. These cells give rise to blood cells of: Myeloid series: Cells arising mainly from the bone marrow. Lymphoid series: cells arising from lymphoid tissues. STEM CELLS These cells have extensive proliferative capacity and also the: Ability to give rise to new stem cells (Self Renewal) Ability to differentiate into any blood cells lines (Pluripotency) They grow and develop in the bone marrow. The bone marrow & spleen form a supporting system, called the “hemopoietic microenvironment” STEM CELLS: Types Pluripotent Stem cells: Has a diameter of 18 – 23 μ. Giving rise to: both Myeloid and Lymphoid series of cells Capable of extensive self-renewal. Myeloid Stem cells: Generate myeloid cells: Erythrocytes Granulocytes: PMNs, Eosinophils & Basophils. Thrombocytes. Lymphoid Stem cells: Giving rise only to: Lymphocytes: T type mainly. Routes a stem cell can take self-renew differentiate CLONAL HEMOPOIESIS MULTIPLICATION COMMITTMENT COMMITTED STEM CELL STEM CELL MULTIPLICATION COMMITTED STEM CELL CFU: COLONY FORMING UNIT CLONAL HEMOPOIESIS: COLONY FORMING UNIT (Contd) (CFU) MORPHOLOGICALLY RECOGNIZABLE MATURE BLOOD CELLS END CELLS: FINITE LIFE SPAN INTERMEDIATE BLAST CELLS Stages in haemopoietic cell development Properties of stem cells 1. Self renewal 2. Hierarchy 3. Extensive proliferative capacity 4. Cell cycle status 5. Surface Markers 6. Interact with microenvironment Stem Cell Hierarchy SITES OF HEMOPOIESIS Yolk sac Liver and spleen Bone marrow –Gradual replacement of active (red) marrow by inactive (fatty) tissue –Expansion can occur during increased need for cell production SITES OF HEMOPOIESIS Active Hemopoietic marrow is found, in children throughout the: Axial skeleton: Cranium Ribs. Sternum Vertebrae Pelvis Appendicular skeleton: • Bones of the Upper & Lower limbs In Adults active hemopoietic marrow is found only in: •The axial skeleton •The proximal ends of the appendicular skeleton. Sites of Hemopoiesis Hemopoiesis starts as early as yolk sac development. 2-3 weeks after fertilization 3 layers are developed (ecto, meso, and endoderm) Hemoangioblast which is derived from the mesoderm Hemoangioblast Endothelial stem cell Hemopoietic stem cell Will develop to Blood vessels will develop to Blood cells In the embryo 2 week old embryo, hematopoiesis begins in yolk sac. THE 1ST CELL TO BE PRODUCED IS erythrocytes By 2 month old fetus, granulocyte and megakaryocyte production. 4th month, lymphocytes production. 5th month, monocytes produced. CONTINUED….. In the 3rd to 7th month of fetal life Hemopoietic stem cells will migrate to the liver and spleen, where hemopoiesis starts there and hemopoiesis is still mainly erythropoietic in nature, with minimal granulopoiesis The bone marrow (BM) The stem cells then migrate to the bone marrow (BM) where hemopoiesis starts and continue all over the life. In the bone marrow all types of blood cells are formed which include: RBCS Granulocytes: Neutrophils, Eosinophils, Basophils Lymphocytes Monocytes and macrophages Platelets Extramedullary Hemopoiesis When required, yellow marrow can be replaced by red marrow. Liver & spleen can aslo resumed. This will multiply the production by 6. Remark that Hemopoiesis within the marrow is called intramedullary or medullary hemopoiesis Cell hierarchy (Haemopoiesis schematic representation) Haemopoietic growth factors Haemopoietic growth factors The haemopoeitic growth factors are glycoprotein hormones that regulate the proliferation and differentiation of haemopoietic progenitor cells and the function of mature blood cells. T lymphocytes, monocytes, marcrophages and stromal cells are the major sources of growth factors except for erythropoietin, 90% of which is synthesized in the kidney and thrombopoietin, made largely in liver. Haemopoietic growth factors GM-CSF Granulocyte-Macrophage colony stimulating factor M-CSF Macrophage colony stimulating factor Erythropoietin Erythropoiesis stimulating hormone (These factors have the capacity to stimulate the proliferation of their target progenitor cells when used as a sole source of stimulation) Thrombopoietin Stimulates megakaryopoiesis Haemopoietic growth factors Cytokines IL 1 (Interleukin 1) IL 3 IL 4 IL 5 IL 6 IL 9 IL 11 TGF-β SCF (Stem cell factor, also known as kit-ligand) Cytokines have no (e.g IL-1) or little (SCF) capacity to stimulate cell proliferation on their own, but are able to synergise with other cytokines to recruit nine cells into proliferation Role of growth factors in normal haemopoiesis Regulation of Haemopoiesis Local environmental control Stromal cell mediated Haemopoiesis Apoptosis Haemopoietic growth factors (Humoral regulation) Mechanism of apoptosis Assessment of hemopoiesis Hemopoiesis can be assessed clinically by; 1- (FBC, CBC= complete blood count) on peripheral blood. 2- Bone marrow Aspiration also allows assessment of the later stages of maturation of hemopoietic cells. 3- Bone marrow Trephine Biopsy provides a core of bone and bone marrow to show architecture. Bone marrow Aspiration Bone marrow aspiration Hypercellular Normocellular Hypocellular