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Blood - Origins

Organisation of the Body

QuestionAnswer
Physiological challenges of blood Distribution of nutrients and waste Defence against pathogens Defence against cellular treason Automatic repair of punctures Dealing with increased organism size Dealing with changes in medium composition
Structural and cellular adaptations of porifera Gas exchange with seawater Nutrients from medium Continuous perfusion Reticulation of internal voids (spongocoel) Defence and homeostasis by phangoytes
Totipotency of phagocytes Archaeocyte is the totipotent cell of sponges - can form all other cells E.g. forms ovum and choanocyte (which forms sperm)
Blood cells from the endothelium Endothelial cells are CD31+ CD44+ endothelial cells are produced from these by rnx1 signalling These are in the dorsal aorta and from erythromyeloid precursors These form fetal erythrocytes and macrophages
Three waves of haematopoiesis Primitive wave from yolk sac endothelium - forms microglia in brain Definitive waves sequentially in dorsal aorta and bone marrow Use mouse models to visualise
Sites of haematopoesis - fetal 0-2 months - yolk sac and dorsal aorta 2-7 months - liver and spleen 5-9 months - bone marrow
Sites of haematopoiesis - infants Bone marrow (practically all bones) - Dwindling post parturition contribution from liver/spleen that ceases in first few months of life
Sites of haematopoiesis - Adults Vertebrae Ribs Sternum Skull Sacrum Pelvis Proximal ends of femur
Stem cells and progenitors Stem cells are unspecialised, can divide and renew for long periods of time Can be induced to become differentiated cells with specialised functions - specific signals Developmental bottleneck - protects from cancer as only certain cells can divide
Evidence for stem cells Took marrow from a mouse femur and counted the cells Irradiate another mouse to kill bone marrow Inject the marrow into the mouse - they repopulate the blood Can count cells via removal of spleen or repeat experiment Showed CD34+ cells are HSC
Blood cell development from bone marrow Perivascular stromal cells support stem cells by secreting 2 proteins that are growth factors for stem cells Stem cell niche is red bone marrow of long bones
Simple process of haematopoiesis HSCs triggered to form multipotent progenitor and common myeloid/lymphoid progenitors by growths factors/cytokines E.g. erythropoietin for RBC Triggers transcription factors in cells to activate specific genes - forces differentiation
Transplanting blood stem cells - when to use Allogenic - acute leukaemia, myeloid leukaemia, lymphoma, anaemia, SCA, thalassaemia Autologous - Lymphoma, Myeloma
Transplanting blood stem cells - process Bone marrow aspirated from iliac crest or leukapheresis of stem cells from peripheral blood after chemo and G-CSF factors Remove residual tumour cells e.g. monoclonal antibodies Infused intravenously after high dose chemo Support therapy e.g. red cells
How peripheral blood stem cells are collected Patient connected to machine Whole blood pumped into the machine Constant centrifuging of the blood isolated the white cells to be collected in bags Rest of blood returned to the body
Potential future methods of transfusion Genetic from HSC - correct genetic errors e.g. by CRISPR of a patients stem cells to remove the disease, transfuse into the patient Developmental by human induced PSC - ne need to collect cells as any nucleated cell can be use to form blood cells
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