L10.1 Muscle regeneration

Question 1

Features of muscle regenerations

Answer 1

• Muscle regeneration peaks at ~14days post-injury; Fibrosis from ~2-4 weeks
• Viable Fibre portion seals off site of injury
• Inflammation dictates success of regeneration
• Ageing prolongs inflammatory marker expression after injury (IL6 & TNF-α)
  
  • Interferes with optimal muscle regeneration

Question 2

Process of muscle regeneration

Answer 2

• Initial injury → hypercontraction (several hours) → Vesicle clumping (1d) → 2o injury (2-5d) → Regeneration (5d) → Myotubes (1-2w) → Recovery (1mth)
  
  • Myofibre formation, where possible, regeneration guided by extracellular structures
    
    • Basal lamina forms scaffold for MF formation
    • But if basal lamina is damage → MT formation is impaired

Question 3

What is the maturity gradient

Answer 3

• MF formation/maturation follows a gradient
• Advance at surviving fibre stump, less mature at centre of injury
• Internal reorganisation & protein synthesis forms new fibres (Myofibrillogenesis)
• Maturation of protein isoforms
• Synthesis of new basal lamina

Question 4

What is the rate of regeneration dependent on

Answer 4

• Extent of injury/muscles injured
• Model (species & metabolism rate), smaller animals respond quicker
• Differential expression of transcription factors, MRF, GF
• Others:
  
  • Recurring injuries
  • Blood supply
  • Inflammatory response
  • Host env (MAJOR DETERMINANT)
  • Neural functions (Not supplied with N → compromised regen)
  • Genetics

Question 5

How does nerve innervation affect muscle regeneration?

Answer 5

• Bupivaccaine treatment → anaesthetic which damages muscle fibres but unhinder nerve innervations → ↑regen (↓force deficit in young & old)
  
  • Also provides protection from 2nd bout → ↓the force deficit

Question 6

What happens during early regeneration (7-14 days)

Answer 6

• Early regeneration:
  
  • 7 days post damage → Fast twitch (EDL) have slow characteristics, vice versa
  • 14 days post damage → Fibre phenotype assured, fast becomes fast, vice versa

Question 7

What is true functional restoration?

Answer 7

• Length-tension relationship restored after ~60 days
  
  • Takes longer for slow muscles

Question 8

Enhancement of muscle repair

Answer 8

• Anti-fibrotic Drugs → could inhibit fibrosis caused by TGF-β1
  
  • If used in conjunction with muscle regen promoting drugs (IGF1) → may be very successful
• Cell therapy
• Tissue engineering strategies