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Regeneration - healing
Regeneration: growth of cells to replace lost structure. Tissue scaffold intact Healing: Tissue response to wound, inflammatory process, or to cell necrosis. Tissue scaffold damaged.
Cell population determined by - proliferation myocytes, neuron is terminal (permanent) hepatocytes if needed (stable tissue) epithelial cell, always new (labile) - differentiation -death by apoptosis stimulated by physiologic, pathologic condition
Stem cells
Characterized by prolonged self renewal capacity and by asymmetric replication ( in every cell division, one of the cells retains its selfrenewing capacity while the others enters a differentiation pathway and converted to a mature population) 1. first identified: embryonic stem cells (pluripotential cells) 2.adult stem cells
Embryo contain pluripotent ES which can rise to all tisue of human bodies . Can be isolated from blastocyst (32 cell group)
Epidermal stem cell: in the bulge of hair foll Intestinal stem cells: at the base of colon crypt, above Paneth cell Liver stem cells (oval cells): in canal of Hering (connected the bile duct and parenchym cells) Corneal stem cells: in limbus (between cornea and conjunctiva)
Liver: liver stem cells functions if hepatocyte proliferation is blocked. After partial hepatectomy or necrotizing injury, hepatocytes them cells proliferate and stem cells are not activated. In fulminant or chronic hepatitis and cirrhosis, when hepatocytes proliferation is blocked, oval cells proliferation is prominent
Skeletal and cardiac muscle: myocytes do not generate. Regeneration of skelet muscle occur in the form of proliferation of satellite cells, that generate differentiated myocytes after injury. Placed in different environment, satellite cells can be osteogenic or adipogenic.
Epithelial tissue: intermediate cells are highly proliferative and terminally differentiated cells do not divide and continously lost of the surface.
Brain: old dogma that NO neuron are generated in adult mammals. Neural stem cells found in olfactory bulb and in dentate gyrus of hypocampus (protein nest in is the histologic marker)
Polypeptide growth factors functions: stimulates cell proliferation cell locomotion differentiation angiogenesis
EGF: mitogenic for variety of epithelial cell, hepatocytes. Healing wound. TGF-alfa: involved in proliferation of epithelial cell in embryo and adult and also malignant transformation of normal to malignant cells. Fibroblast GF: angiogenesis, hematopoesis, skeletal muscle development, wound repair
HGF(hepatocyte Growth factor): mitogenic effects in most epithelial cells, incl. Hepatocytes and biliary epithelium VEGF (Vascular endothelial GF): potent inducer of blood vessel formation/vasculogenesis and new blood vessel (angiogenesis)
Platelet Derived GF: migration and proliferation of fibroblast, macrophages, and monocytes
First: binding of signaling molecule (ligand) to cell receptors Based on the source of ligand and the location of its receptor (same, adjacent, or distant cells) there are three modes of signaling: autocrine, paracrine, and endocrine.
Autocrine signaling
Cell respond to the signaling molecules that themselves secrete For examples: - liver regeneration - proliferation of antigenstimulated lymphocytes Tumour frequently overproduces GFs and their receptors
Autocrine signaling
Paracrine signaling
One cell type produce the ligand which then acts on adjacent target cells that express the appropriate receptors.
Common in wound healing. Factor produced by one cell type (eg macrophage)has growth effects on adjacent cell (*eg.fibroblast)
Paracrine signaling
Endocrine signaling
Hormone ia synthesized by cells of endocrine organ and act on the target cells distant of their sites of synthesis. GF, eg HGF may also circulate and acts on distant sites.
Endocrine signaling
Macromolecule outside cells 1. fibrous structural protein collagen, elastine 2. adhesive glycoprotein 3. proteoglycans, hyaluronic acid
Several adhesion molecules play in part of leucocytes migration, homing, and cell to cell interaction.
Angiogenesis
In embryo: vasculogenesis, formed by endothelial precursor cells (EPCs, angioblast) In adult: angiogenesis (neovascularization): -branching of adjacent blood vessel -recruitment of angioblast from bone marrow Critical for:-chronic inflammation -tumour growth -vascularization of ischaemic tissue
VEGF, stimulates the mobilization of ECP from bone marrow. Proliferation and differentiation in the site of angiogenesis PDGF, TGF-beta:stabilize the new vessel via formation of ECM cytokines Hypoxia.
Fibroblast emigration and proliferation, which is triggered by GFs TGF-beta, PDGF, FGF, EGF, cytokines IL-1 and TNF.The source of this GFs is inflammatory cells. Incresed synthesis of collagen, decreased of ECM by MMP.