Session 4: Regeneration and Repair Flashcards
Wound healing involves three processes. Which?
Haemostasis
Inflammation
Regeneration
There are three main factors of which cells are induced to regenerate. Which?
Growth factors
Cell-cell communication
Electric current and nervous stimuli
What three groups can tissues of the body be divided into based on their proliferative activity/regeneration?
Labile tissues
Stable tissues
Permanent tissues
Explain labile tissues and give examples.
Proliferation of cells throughout life in these tissues which replace cells that are destroyed.
Surface epithelia Lining mucosa Columnar epi of GI tract and uterus Transitional epithelium of urinary tract Cells of bone marrow Haemopoietic tissue
Explain stable tissues and give examples.
Also called quiescent tissues. Normally a low level of replication but can undergo rapid proliferation in response to stimuli. This means that the cells are usually in G0 but can go to G1 in case of stimuli.
Parenchymal cells of the liver, kidneys and pancreas.
Mesenchymal cells such as fibroblasts, bone osteoclasts and smooth muscle cells.
Vascular endothelial
Resting lymphocytes
White blood cells
Explain permanent tissues and give examples.
Tissues containing cells that have left the cell cycle and will not divide anymore. This means that any damage to permanent tissue will lead to healing with scar tissue or in case of the CNS microglial cells will fill the cavity.
Neurones
Skeletal muscles
Cardiac muscle
What are stem cells and what are their roles?
Cells with prolonged proliferative activity which show asymmetric replication. They differentiate into mature non-dividing cells and are involved in tissue regeneration in tissue where regeneration is possible.
What is asymmetric replication?
When one stem cells stays a stem cell and the other one goes on to differentiate into the desired cell type.
Give some example of different ‘grades’ of stem cells. What are they and where are they found?
Totipotent which can differentiate into any cell only found in embryo.
Multipotent which can differentiate into a lot of different cells, can be found in adult stem cells, an example is haemopoietic stem cells (HSC).
Unipotent which differentiate into one specific lineage. This is the most common stem cell in adult stem cells.
Give the regenerative capacity of the following tissues:
- Bone
- Tendons
- Articular cartilage
- Adipocytes
- Epithelia
- Liver
- Mesothelia
- Smooth muscle
- Striated muscle
- Peripheral nerves
- CNS
- Very good
- Poor
- Poor
- None
- Very good
- Very good
- Good
- Very good
- Poor to none
- Poor
- None
Why would fibrous repair occur?
If the collagen framework of a tissue is destroyed, in case of chronic inflammation, in case of necrosis of specialised parenchymal cells that cannot be replaced -> fibrous repair will be initiated leaving a scar behind.
Outline the steps of fibrous repair.
- Phagocytosis of debris
- Proliferation of endothelial cells result in angiogenesis (formation of small capillaries).
- Proliferation of fibroblasts and myofibroblasts -> collagen synthesis and deposition and wound contraction. This forms granulation tissue.
- Granulation tissue becomes less vascular and mature into a fibrous scar.
- Scar matures and shrinks by contraction of fibrils in myofibroblasts.
Briefly outline collagen features.
Triple helix of alpha chains.
Gly-x-y repeating sequence.
Cross-linking between alpha chains strengthen the collagen.
Give examples of diseases due to collagen defects.
Scurvy - vitamin C def. for hydroxylation of procollagen -> unable to heal wounds adequately
Ehlers-Danlos Syndrome - Collagen fibres lack adequate tensile strength.
Osteogenesis imperfecta - Too little bone tissue and extreme skeletal fragility
Alport syndrome - X-linked disease. Abnormality in Type 4 collagen resulting in dysfunction of the glomerular basement membrane, cochlea of the ear and lens of the eye. Haematuria follows and chronic renal failure eventually. Neural deafness and eye disorders.
Symptoms of EDS.
Hyperextensible skin Fragile skin Skin susceptible to injury Poor wound healing Hypermobility of joints Rupture of colon and large arteries Corneal rupture and retinal detachment
What kinds of cell communications are responsible for regeneration and repair?
Autocrine - the cell responds to signalling molecules that they produce themselves
Paracrine - adjacent cells produce local mediators which act on adjacent cells.
Endocrine - release of hormones by endocrine organ released into blood stream and act on distant tissue.
What else besides local mediators are important in tissue repair and regeneration?
Growth factors.
Give structure and features of growth factors. What are their roles?
Polypeptides that act on specific cell surface receptors. Also called local hormones. Stimulate cell proliferation or inhibition and regulate the entry of the cell into the cell cycle and the cell's passage through the cell cycle. Also affect: Cell locomotion Contractility Differentiation Viability Activation Angiogenesis
Give examples of growth factors.
Epidermal growth factor
Vascular endothelial growth factors
Platelet-derived growth factors
Tumour necrosis factors
What are epidermal growth factors? What do they do and how are they produced?
Stimulate mitosis for epithelial cells, hepatocytes and fibroblasts.
They are produced by keratinocytes, macrophages and inflammatory cells.
What are Vascular endothelial growth factor? What do they do and how are they produced?
Stimulates vasculogenesis and angiogenesis in tumours, chronic inflammation and wound healing.
What are Tumour necrosis factor? What do they do and how are they produced?
Stimulates fibroblasts migration, proliferation and collagenase secretion.
Another concept in wound healing that is important is contact inhibition. What is contact inhibition?
When normal cells become isolated from other cells they will start to replicate until they touch another cell. This forms a monolayer sheet of cells with no cell overlap. Adhesion molecules play an important role
What are adhesion molecules that bind to each other called?
Cadherins
