Regeneration And Repair Flashcards
What are stem cells?
- Limitless proliferation
- Daughter cells either remain as stem cells to maintain stem cell pool or differentiate
- Internal repair system to replace lost/damaged cells in tissues
What is regeneration?
- Replacement of dead or damaged cells by functional, differentiated cells (derived from stem cells)
What are labile cells?
- Rapid proliferation
- State is active cell division G1-M-G1
- E.g epithelial/haematopoietic cells
What are stable cells?
- Variable regeneration speed
- E.g hepatocytes/osteoblasts
What are permanent cells?
- Unable to divide
- Unable to regenerate
What are the factors controlling regeneration?
- Growth factors
- Contact between basement membrane and adjacent cells
How do growth factors control regeneration?
- Promote proliferation in stem cell population
- Extracellular signals transduced into the cell
- Promotes expression of genes controlling cell cycle
- Hormones: oestrogen/testosterone/GH
- Autocrine/paracrine/endocrine signals from many cell types
How does contact between basement membranes and adjacent cells control regeneration?
- Signalling through adhesion molecules
- Inhibits proliferation in intact tissue
- Contact inhibition
- Loss of contact promotes proliferation
- Mech is deranged in cancer
What is fibrous repair?
- Replacement of functional tissue by scar tissue
What are the 3 main parts of fibrous repair?
- Cell migration
- Blood vessels - angiogenesis
- ECM production and remodelling
- These initiate fibrous repair by combining to form granulation tissue
What are the main cell types in fibrous repair
- Inflammatory cells: phagocytosis of debris - neutrophil/macrophages
chemical mediators - lymphocytes and ^ - Endothelial cells: angiogenesis
- Fibro/myofibroblasts: ECM proteins e.g collagen
wound contraction
What is angiogenesis?
- Blood supply development is vital to wound healing
- Provides access to the wound for inflammatory cells and fibroblasts
- O2 and nutrient delivery
- Endothelial proliferation induced by pro-angiogenesis GF e.g VEGF
- Pre existing blood vessel sprout new vessels
- Mech exploited by malignant cells
Outline the process of angiogenesis.
- Endothelial proteolysis of basement membrane
- Migration of endothelial cell via chemotaxis
- Endothelial proliferation
- Endothelial maturation and tubular remodelling
- Recruitment of peri-endothelial cells
What is the role of the extra cellular matrix in fibrous repair
- Supports and anchors cells
- Separates tissue compartments e.g basement membrane
- Sequesters GF
- Allows communication between cells
- Facilitates cell migration
What is the role of collagen in fibrous repair?
- Provides extracellular framework
- Composed of triple helices of various polypeptide alpha chains
- Remodelled by specific collagenates
How are fibrillar collagens I-III synthesised?
- Polypeptide alpha chains are syn. in ER
- Enzymatic modifications (Vit C dependent hydroxylation)
- Alpha chains align and cross-link forming the procollagen triple helix
- Soluble procollagen in secreted
What diseases are due to defects in collagen synthesis?
- Vit C deficiency (scurvy)
- Ehlers-Danlos syndrome (defective conversion of procollagen to tropocollagen)
- Osteogenesis imperfecta
- Alport syndrome
What is present in the ECM and what does it do?
- Matrix glycoproteins: organise and orientate cells, support cell migration
- Proteoglycans: matrix organisation, cell support, regulate GH availability
- Elastin: tissue elasticity
What are the 3 steps of the fibrous repair mechanism?
- Inflammatory cell infiltrate
- Clot replaced by granulation tissue
- Maturation
What happens in inflammatory cell infiltration?
- Blood clot forms
- Acute inflammation around the edges
- Chronic inflammation: macrophages and lymphocytes migrate into clot
What is meant by ‘clot replaced by granulation tissue’?
- Angiogenesis: capillaries and lymphatics sprout and infiltrate
- Myofibroblasts migrate and differentiate
- ECM produced by (myo)fibroblasts
What is maturation?
- Cell population falls
- Collagen levels increase, matures and remodels
- Myofibroblasts contract reducing volume of defect
- Vessels differentiate and are reduced
- Result: fibrous scar
How are the inflammatory cells recruited for repair?
- Chamotaxis
What is healing by primary intention?
- Incised wound
- Apposed edges (fall back on each other)
- Minimal clot and granulation tissue
- Epidermis regeneration
- Dermis undergoes repair
How can primary wounds be aided in healing?
- Sutures for ~10 days
- Then at about 10% of normal strength
In a clean sutured wound how long will maturation take?
- ~2 years
When may a secondary wound occur?
- Infarct
- Ulcer
- Abscess/large wound
What is healing by secondary intention?
- Unapposed edges
- Clot forms -> scab (ESCHAR)
- Epidermis regeneration from base up
- Repair process produces MORE granulation tissue
If there is a bone fracture. What is the first step of bone fracture repair and why is this organised?
- Haematoma
- Framework for macrophages, endothelial cells, fibroblasts and osteoblasts
Outline the full process of bone fracture repair.
- Necrotic tissue removed
- Capillaries develop
- Specialised maturation of cells -> callus
- Bone laid down in irregular woven pattern and islands of cartilage
- External callus provides splint-like support
- Woven bone gradually replaced by more organised lamellar bone
- Lamellar bone gradually remodelled to direction of mechanical stress
What are the local factors influencing wound healing?
- Type/size/location of wound
- Apposition/lack of movement
- Blood supply
- Infection
- Foreign material
What are the general factors influencing wound healing?
- Age
- Drugs hormones
- Dietary deficiencies
- Health state
- CV status
What are the possible complications of repair and why?
- Insufficient fibrosis: wound dehiscence (falling apart): hernia/ulceration/obesity/malnutrition/steroids/elderly
- Excessive fibrosis: cosmetic scarring: keloid/cirrhosis
- Excessive contraction: obstruction of tubes and channels (strictures)
