Tissue Renewal, Repair, and Regeneration

Question 1

Describe tissue regeneration

Answer 1

Replacement of injured tissue with cells of the same type & function

Question 2

Describe tissue repair

Answer 2

Occurs when extent or nature of damage cannot be revered by regeneration alone

Question 3

Differentiate tissue regeneration and tissue repair

Answer 3

Tissue regeneration:
- Injured tissue replaced by OG cell type
- organ functions the same
- no scarring
Tissue repair:
- Injured tissue replaced by fibroblasts
- Organ does not function the same
- Causes scarring

Question 4

List the 4 stages of healing after tissue injury

Answer 4

Hemostasis
Inflammation
Proliferation
Remodeling

Question 5

What is the goal of hemostasis?

Answer 5

to stop bleeding & create the scaffold for migrating cells

Question 6

Describe hemostasis

Answer 6

• Occurs in minutes
• Results in local vasoconstriction and activation of platelets and clotting factors to form a fibrin clot
• This creates the scaffold for migrating cells

Question 7

What is the goal of inflammation?

Answer 7

to kill bacteria & clean the wound on the inside

Question 8

Describe inflammation

Answer 8

• Occurs in hours
• Driven by platelet-derived mediators, bacteria, and secreted chemoattractants

Question 9

What is the goal of proliferation?

Answer 9

to replace lost/injured tissue

Question 10

Describe proliferation

Answer 10

• Occurs in days
• Mediated by macrophage and fibroblast-derived growth factors
  -> Proliferate the cell types that have been lost
  -> Endothelial cells for skin wounds

Question 11

What is the goal of remodeling?

Answer 11

to restore the tensile strength of tissue
-> “framing” of new tissue

Question 12

Describe remodeling

Answer 12

• Occurs in weeks to months
• Transition from type III to Type I collagen
• Restores tensile strength of tissue

Question 13

What does complete injury healing require?

Answer 13

BOTH proliferation & remodeling

Question 14

List the determinants of regeneration versus repair after tissue injury

Answer 14

• nature of cells injured
• extent of injury
• presence of ongoing inflammation
• underlying disease

Question 15

Why does the nature of cells injured determine regeneration versus repair after tissue injury?

Answer 15

some cells have marginal renewal capacity

Question 16

Why does the extent of injury determine regeneration versus repair after tissue injury?

Answer 16

the magnitude of injury may exceed regeneration capacity

Question 17

Why does the presence or absence of ongoing inflammation determine regeneration versus repair after tissue injury?

Answer 17

Continued release of inflammatory mediators may disrupt balance toward repair
-> Can be due to concurrent infection or other factors

Question 18

Why does underlying disease determine regeneration versus repair after tissue injury?

Answer 18

Underlying disease(s) may impair proliferative response or remodeling
(example = diabetes)

Question 19

State the common outcome of various signal transduction pathways of growth factors

Answer 19

Growth factors interact with a variety of surface receptors & activate transcription factors
-> Causes cell proliferation

Question 20

Name ONE common growth factor

Answer 20

Epidermal Growth Factor (EGF)

Question 21

Name source(s) of epidermal growth factor

Answer 21

Activated macrophages, keratinocytes, and many other cells

Question 22

Name function(s) of epidermal growth factor

Answer 22

• Mitogenic for keratinocytes and fibroblasts
• Simulates keratinocyte migration & granulation tissue formation

Question 23

Describe the two forms of extracellular matrix (ECM)

Answer 23

There are two forms, located in the Basement Membrane & Interstitial Matrix, respectively

Question 24

List the key components of ECM located in the basement membrane

Answer 24

Type 4 collagen
Laminin
Proteoglycan

Question 25

List the key components of ECM located in the interstitial matrix

Answer 25

Fibrillar collagens
Elastin
Proteoglycan & hyaluronan

Question 26

Name a difference between the ECM located in the basement membrane & the ECM located in the interstitial matrix

Answer 26

• Interstitial matrix needs to have more give / move / flexibility than basement membrane
• Basement is more structural

Question 27

What is an important molecule for the ECM

Answer 27

INTEGRIN !!

Question 28

List the 3 key growth factors that regulate fibrosis

Answer 28

PDGF (platelet-derived growth factor)
TGF-beta (transforming growth factor)
FGF-2 (fibroblast growth factor)

Question 29

Describe the result of PDGF (platelet-derived growth factor

Answer 29

Migration & proliferation of fibroblasts smooth muscle cells & macrophages

Question 30

Describe the result of TGF-beta (transforming growth factor)

Answer 30

• Potent fibrinogenic factor that stimulates collagen, fibronectin and proteoglycan synthesis
• Inhibits collagen degradation
• Inhibits lymphocyte proliferation
• Has anti-inflammatory effect

Question 31

Describe the result of FGF-2 (fibroblast growth factor)

Answer 31

• Stimulates proliferation of endothelial cells
• Promotes migration of macrophages and fibroblasts to damaged areas