Lecture 8- Healing, regeneration and repair

Question 1

What is the difference between regeneration and repair?

Answer 1

Regeneration is the replacement of lost cells by those of the same kind while repair requires the use of temporary granulation tissue which will eventually lead to the formation of a scar

Question 2

What type of injuries can be repaired through just regeneration?

Answer 2

Injuries which involve loss of the epithelial lining only, if the stromal or parenchymal tissue is lost then a full scale repair mechanism will need to be mounted

Question 3

What causes the regeneration response?

Answer 3

Stem cells

Question 4

What are the three types of tissue activity with regards to regeneration and stem cells?

Answer 4

Mitotically active tissues which regenerate constantly such as the lining of the gut
Normally quiescent tissues which only undergo regeneration when there is an injury
Terminally differentiated tissues which cannot undergo regeneration

Question 5

What stimulates regeneration in colon crypts?

Answer 5

LPS activates TLR4 on macrophages which activates COX2 Which activates PGE2

Question 6

How do Kupffer cells induce hepatic regeneration?

Answer 6

Release of TNF, IL-6, HGF and TGFalpha

Question 7

What are kupffer cells?

Answer 7

Macrophages present in the liver

Question 8

What transcription factors can induce terminally differentiated cells to once gain become pulripotent?

Answer 8

Oct4, Sox2, Klf4, Myc

Question 9

What occurs in haemostasis?

Answer 9

Platelets aggregate and degranulate at sites of blood vessel damage, conversion of fibrinogen to fibrin with cross linke between fibrin being made by fibronectin and other transglutaminases

Question 10

What is the purpose of haemostasis?

Answer 10

To provide temporary mechanical stability, to provide a barrier for invading microorganisms, prevent dessication and loss of plasma, provides a provisional matrix for repair cells to migrate, generates a matrix rich in cytokines and growth factors (platelet derived growth factor, TGFbeta, Vascular endothelial growth factor)

Question 11

What occurs in the inflammatory response?

Answer 11

Removal of necrotic tissue through the actions of both neutrophils and macrophages
These secrete proteases which liquify the necrotic tissue, generate antimicrobial products such as free radicals

Question 12

What actions in the inflammatory response occurs ONLY via macrophage activity?

Answer 12

Phagocytosis of dead neutrophils

Secretion of growth factors for fibroblasts and endothelial cells, antigens are processed to activate immunity

Question 13

What occurs in the proliferation response?

Answer 13

Stromal and epithelial tissue regrows

Fibroblasts proliferate and form a new matrix out of collagen, fibronectin and glycosaminoglycans

Question 14

What occurs to fibroblasts in the proliferation phase of repair?

Answer 14

They differentiate into myofibroblasts when stimulated by Platlet-derived-growth factor and transforming growth factor which interact with ED-A Fibronectin which results in provision of mechanical tension

Question 15

What are the functions of myofibroblasts?

Answer 15

Lay down collagen fibers, express alpha smooth muscle actin, smooth muscle myosin and contractile myofilaments
Use focal adhesions to to link stress fibres with extracellular actin
Pull the edges of the wound together through contractile actions
Die by apoptosis at the end of the granulation phase

Question 16

What is the role of endothelial cells in the proliferation phase?

Answer 16

New blood vessels are formed in response to VEGF, pericytes stabilize these in response to PDGF

Question 17

What growth factors allow the epithelial lining to regrow in the proliferative phase of repair?

Answer 17

Epidermal growth factor or transforming growth factor
These upregulate the EGF receptor, cause integrins to be expressed along the cell margin, activation of proteolytic enzymes to break down some of the temporary granulation tissue which has occured

Question 18

What occurs in the remodelling phase of repair?

Answer 18

Granulation tissue is exchanged for scar tissue which lacks cells, collagen III is replaced by parallel collagen, and equilbrium is reached between collagen deposition and MMP degradation, strength of collagen fibres results in crosslinks

Question 19

Excessive scar tissue is damaging, what can cause excessive scar tissue to form?

Answer 19

Excessive inflammatory response, excessive production of fibrogenic cytokines (TGFBeta1), prolonged presence of myofibroblasts as a result of their failure to undergo apoptosis

Question 20

What can cause wound repair to develop into fibrosis?

Answer 20

Silica or smoke in the lungs, Inability to maintain telomers, hypercholesterolemia resulting in liver damage, alcohol abuse or viruses (HBV, HCV) causing liver damage, obstruction of ureter leading to kidney fibrosis

Question 21

What damaging cycle can fibrosis result in?

Answer 21

Fibrosis my suppress blood flow, this can result in cell death due to a lack of oxygen supply which will result in more fibrosis occuring