Lecture 10

1.
What cells have the ability to regenerate?
Epithelial cells on skin or intestinal villi
2.
What is meant by mitotically active all the time?
Bone marrow haematopoietic cells, skin, gut, repiratory, genitourinary epithelium constantly are dividing and regenerating
3.
What stimulates quiesent cells to regenerate?
Injury (eg. liver restores tissues if 70% of tissue is lost)
4.
What is terminally differentiated?
When a cell cannot re-enter the cell cycle and is not replaced (neurons, cardio myocytes)
5.
What is the first step to repair to skin?
Clotting by platelet aggregation and fibrin/fibronectin. Provides stability, barrier, matrix for migration and growth factors (PDGF, TGFbeta, VEGF)
6.
What must occur before tissure repair can proceed?
Removal of necrotic tissue (debridement)
7.
 What is involved with debridement?
Neutrophils and macrophages phagocytose debris, liquify necrotic tissue through proteases, generate ROS, secrete growth factors for fibroblasts and epithelial cells, process antigens
8.
What happens during tissue formation?
Stromal and epithelial cells proliferate. Fibroblasts proliferate and migrate into provisional matrix forming granulation tissue of collagen III, collagen I, fibronectin
9.
What causes fibroblasts to differentiate into myofibroblasts?
In response to PDGF and TGFbeta from platelets and macrophages, mechanical tension, or ED-A fibronectin
10.
What do myofibroblasts do?
Lay down collagen, express alpha smooth muscle actin, focal adhesions, attach to each other and contract to close wound, die by apoptosis after granulation
11.
How do endothelial cells contribute to tissue formation?
Form new capillaries, proliferate and migrate to macrophage VGEF.
12.
What happens during reepithelialisation?
Epithelial cells re-cover the wound
13.
What effect do growth factors such as EGF and TGFalpha have on epithelial cells?
ECs migrate along wound margin, use proteases to move through fibrin, regain their original phenotype when they have formed a continuous layer
14.
What happens in the months of remodelling after tissue formation?
Granulation tissue replace with acellular scar tissue (collagen I bundles replace disorganised collagen III)
15.
When may wound healing fail?
Ischaemia, progenitor cells compromised, ends of bone not brought together
16.
What occurs with excessive scarring?
Keloids (disfigurement), strictures (narrowing of tubes), pain, loss of mobility
17.
What causes excessive (hypertrophic) scarring?= =Excessive inflammatory response, excessive TGFbeta, prolonged presence of myofibroblasts