Wound healing Flashcards
Differentiate tissue regeneration and scar formation
Regeneration
• Proliferation of residual and injured cells, and maturing of tissue stem cells
• Returns injured site to original state
Scar formation
• Deposition of fibrous tissue to enable enough structural integrity for the damaged tissue to continue functioning
List various types of tissues
- Labile
- Stable
- Permanent
Describe the regenerative ability of labile tissues, with examples
• Very proliferative because cells are frequently due to friction
Examples • Oral mucosa • Vagina • Cervix • GI tract columnar epithelium • Fallopian tubes
Describe the regenerative ability of stable tissues, with examples
- Usually, the cells are in a non-proliferate stage
- However, these cells may become activated to proliferate when injury or tissue loss occurs
Examples • Parenchyma (single units) of liver • Endothelial cells • Fibroblasts • Kidney
Describe the regenerative ability of permanent tissues, with examples
• Terminally differentiated non proliferative cells
Examples
• Neurons
• Cardiomyocytes
• Skeletal muscle cells
Give an example of the regenerative ability of intestinal epithelia
- Intestinal epithelia are replaced by proliferation of residual cells and tissue stem cells that mature
- The apex of the epithelium is experiencing friction from faecal matter and toxin exposure
- Thus the stem cells are found at the basement membrane; else they’ll be wiped out with the cells at apex top
Give an example of the regenerative ability of the liver
- Liver can also regenerate from the proliferation of hepatocytes and repopulation by progenitor cells
- Kupffer cells (macrophage like) drive this process via IL-6, while growth factors such as hepatocyte growth factor (HGF) also has a role
- Sometimes, the proliferative capacity of the liver may be impaired. Thus, progenitor cells contribute to repopulation which may reside in specialised canals in the liver known as Hering
Describe the source and role of specific growth factors during the various phases of scar tissue formation
Transforming Growth Factor- a (TGF-a):
* Stimulates proliferation of hepatocytes and many other epithelial cells
• Macrophages
• Keratinocytes
Transforming Growth Factor- B (TGF-B)
• Synthesis and deposition of connective tissue proteins
• Inhibits MMPs so it stops degradation of the ECM
• Macrophages
• Keratinocytes
• Helper T cells
• Platelets
Vascular Endothelial Growth Factor (VEGF)
• Stimulates proliferation of endothelial cells; increases vascular permeability
• Mesenchymal cells
What are the three stages of scar formation?
- Inflammation: acute & chronic
- Cell proliferation
- Remodelling
Describe the role of macrophages and fibroblasts in the inflammation stage of scar formation
Inflammation
• Activated platelets release IL-8 to recruit neutrophils and macrophages
• M1 macrophages clear microbes, necrotic tissue and promote inflammation
• M2 macrophages produce growth factors that stimulate proliferation of many cell types
Describe the role of macrophages and fibroblasts in the cell proliferation stage of scar formation
Cell proliferation
• Fibroblasts, endothelial and epithelial cells proliferate and migrate to new wound
• Epithelial cells produce local growth factors to create a seal over the wound
• Endothelial cells proliferate to form new blood vessels
• Fibroblasts proliferate to lay down collagen at site of injury
• Collectively, this process is termed granulation tissue. It is highly vascular (leaky vessels with tissue oedema) which eventually matures
Describe the role of macrophages and fibroblasts in the remodelling stage of scar formation
Remodelling
• Collagen is deposited to form a fibrosis scar
• Initially, collagen type III fibres are deposited. However, they are unorganised and weaker than type I
• In remodelling, MMP’s resorb the type III collagen and replace it with type I collagen
• Complete wound healed tissue will never reach its optimal strength again
• As the scar matures, there is progressive vascular regression which eventually turns the highly vascular tissue into one that is mostly avascular
Describe the process of angiogenesis
Angiogenesis
• Formation of new blood vessels
• Perfusionis when the blood gets to a tissue so that it can do its job of oxygenating
• Mediated by VEGF-A which stimulates the migration and proliferation of endothelial cells. It also promotes vasodilation via Nitric Oxide production
• MMP’s degrade the ECM to permit remodelling and angiogenesis
How do fibroblasts work to heal wounds
- Fibroblasts enter from the edge and migrate towards the centre of the wound
- Cells may differentiate into myofibroblasts which has contractile activity due to actin filaments
- These myofibrils close the wound by pulling its margin towards the centre
- Fibroblasts and myofibroblasts produce a lot collagen= scar
- They disappear once they have contracted the wound by apoptosis and MMPs
- Eventually, the fibroblasts will assume another phenotype which enables them to redeposit the lost ECM
Describe the role of MMPs, TIMPS and fibroblasts in influencing the ECM and extent of scar tissue formation
- Eventually, connective tissue is degraded by MMPs and scar shrinks
- MMPs are produced by many cell types and their synthesis, secretion and activation is regulated by growth factors, cytokines and reactive oxygen species
- MMP 1: interstitial collagenases which cleave fibrillar collagen
- MMP 2 & 9: gelatinases which degrade amorphous collagen and fibronectin
- MMP 3, 10 & 11: degrade ECM
- Serine proteinases aren’t as important as MMP’s in wound remodelling
- The size of scar tissue is dependant on a balance between MMP and TIMPS
