wafl 4: muscle injury and healing

what was the first identified stem cell?

satellite cells in muscle

where does the satellite cell live?

between the basil lamina and plasma membrane of muscle fibers

what is the satellite cell called?

pax - 7

what do satellite cells do?

regenerate muscle

how do we know that satellite cells regenerate muscle?

based on mice research!

in the mice that had satellite cells entirely removed, muscle regeneration was not possible

how does a satellite cell become muscle?

1) proliferation to repair damage

2) leave satellite cells for future repair needs

3) move to the site of injury

4) differentiate and fuse to damages muscle to form new

what is a niche?

the microenvironment of a cell (physical matrix, soluble chemical signals, and contact with other cells)

what is a physical signal?

when the satellite cell grabs the ECM and pulls with cytoskeletal motors, it can feel matrix stiffness and dynamic movement

what else provides a scaffold for regeneration?

the basil lamina

is the basal lamina intact in a contusion?

yes, this allows regeneration to happen faster

is the basal lamina intact in a laceration?

no, it is disrupted causing a slower regeneration

what are the chemical directions?

1) neutrophil invasion

2) macrophage invasion: chew up damage so space for new muscle

3) Satellite cell division and migration

4) myoblast fusion

what is macrophage polarization?

M1 and M2 working together to send a signal for satellite cells to come heal and build the muscle back up

what does M1 do?

clear debris and dead cells

what does M2 do?

signal the myoblasts to migrate and differentiate

often seen in DOMS

is some inflammation good?

yes, it causes new muscle to be created!

what happens when macrophages are prevented from switching from type 1 to type 2?

muscle regeneration is severely impaired

what are other sources of chemical directions?

- growth factors may be released from the ECM and muscle fibers upon physical damage

- they may also be released during unaccustomed activity which may drive satellite cell response to non-injurious stimuli like endurance training

what happens when the progenitor cells of a tissue are unable to respond sufficiently to injury?

a stiff fibrous scar forms

what are the first responders to injury and what do they do?

fibroblasts (the cells that live in the ECM), they lay down a connective tissue matrix that maintains the tissue structure

do the fibroblasts repair the injury?

technically, but the new tissue doesn't function quite as well as it did before, unless the progenitor cells are able to come in and rebuild

what is exercise induced injury?

during eccentric contractions, the muscle experiences high forces that microdamage the sarcomeres

how are exercise induced injuries healed?

they can be repaired by the myofiber alone or with assistance of satellite cells

what is the result of exercise induced injury?

- delayed onset muscle soreness

-hypertrophy

when is a strain or pull likely to occur?

following an eccentric contraction, but also with external forces like a high velocity fall or joint dislocation

what happens to myofibers during a strain or pull?

myofibers are completely torn, typically thru one or more fascicles

how is a strain or pull repaired?

not by the myofiber alone, requires satellite cells

treatment: PRICE

depending on the degree of tearing, the muscle will fully regenerate or scar

what is a laceration and contusion?

an injury that is common with contact sports and car accidents, it is anything that hits your muscle really hard

when the force is sharp is it a laceration or contusion?

laceration: cuts thru myofibers

when the force is dull is it a laceration or contusion?

contusion: crushes myofibers

how are lacerations and contusions repaired?

SATELLITE CELLS

treatment: PRICE, unless the laceration is substantial enough to require surgical closure

fibrotic scarring is common

when is volumetric muscle loss common?

military personnel in conjunction with IED blast, but also in car accidents

large portions of muscle volume are destroyed

how is volumetric muscle loss repaired?

satellite cells cannot overcome this degree of damage and the muscle is irretrievably lost and replaced with a fibrotic scar

what is duchenne muscular dystrophy?

the absence of dystrophin makes muscle fibers fragile, which means the fibers are repeatedly chronically injured during everyday activity

in duchenne muscular dystrophy, what is healthy muscle replaced with?

ECM (fibrosis) and fat, this results in a progressive loss of function

is satellite cells proliferation and differation reduced in DMD?

YES

is there a limit on the number of times satellite cells can renew themselves?

yes

what eventually happens to satellite cells?

they become senescent and are unable to respond well to injury cues

why arent donor satellite cells good for DMD?

the human body might reject them, a mouse is not a person, limited amount of donor material

what happens to satellite cells when you age?

the numbers and activity are reduced

what type of inflammation is aging associated with?

chronic low-grade inflammation, also a decrease in androgens, growth factors

when mechanical stretch happens, what increases?

satellite cells increase proliferation

how does treadmill running impact a contusion injury?

it increases the contribution of injected satellite cells to repair the contusion injury

how developed is regenerative rehab?

it is in its infancy