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Muscle & Exercise Physiology > Lecture 20 - Myogenesis: from stem cells to to muscles > Flashcards

Lecture 20 - Myogenesis: from stem cells to to muscles Flashcards

1
Q

True or False

muscle can regenerate itself

A

true

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2
Q

POst-natal myogenesis follows a similar path to that of embryonic myogenesis, the main difference being the starting cell is a _____

A

satellite cell

muscl regeneration/repair is mediated by a population of resident adult stem cells termed satellite cells

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3
Q

Describe satellite cells, how the are activated, what they express, where they reside.

A

Quiescent cell population capable of synthesizing mulscle

activated in response to damage

Distinct from myonuclei -reside between the plasma membrane and the basal lamina (referred to as the satellite cell niche)

heterogeneous population

lineage negative, not expressing markers specific to any type of cell (MyoD-, CD45-, Sca1-)

Express Pax7, Pax3, CD34 = muscle precursor cells (same things expressed)

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4
Q

describe the muscle stem cell niche.

A

defined anatomical location between the muscle fibre and the basal lamina

localised close to BVs

allows systemic regulation of satellite cell activity

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5
Q

What are the two theories of how satellite cells self renew?

A

Theory A - asymmetric cell division

Satellite cell divides to form one new quiescent satellite cell whihc populates the niche, and one activated satellite cell which enters the cell cycle and proliferates

Theory B - return to quiescence

Satellite cell becomes activated and proliferates after which one cell will return to quiescence and repopulate the niche

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6
Q

True or false

in adults we don’t usually see the formation of new muscle fibres

A

truw

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7
Q

True or False

In the adult, Pax3 expression is maintain in all satellte cells and proliferating myoblasts, and decreased rapidly prior to differentiation

A

False

this is Pax7

Pax 3 is co-expressed in satellite cells only in the diaphragm and body wall muscles

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8
Q

True or false

If you don’t have Pax7 you don’t have satellite cells

A

true

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9
Q

Damaged muscle fibres release ___ ____ ______ which is known to activate satellite cells

A

hepatocyte growth factor

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10
Q

What is atrophy related to old age?

A

sarcopenia

dystrophy = genetic disease

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11
Q

Why do satellite cells fail to continue regeneration?

A

Limited ability to regenerate after a certain age?

Changes in local/systemic environment no longer favour regeneration?

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12
Q

What is the evidence for and against the statement that “Satellite cells wear out’’?

A

Old muscles don’t regenerate as well as young muscles

satellite cell number may/may not decrease with age and after repeated cycles of degeneration/regeneration (such as in muscle disease)

Old muscles can regenerate weill if placed in a ýoung’environment - indicates that loss of regenerative capacity (at least in aging) is not due to the loss of satellite cells but due to changes in the EC environments (i.e hormones, growth factors etc)

You will wear out long before your satellite cells do!

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13
Q

Young muscles transplanted into old mice ___ regenerative ability

A

lose

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14
Q

old muscles transplanted into young mice ___ regenerative ability

A

gain

it must be systemic changes (circulating factors) in the rat itself that make it lose the ability to regenerate

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15
Q

True or False

satellite cells are capable of forming new muscle fibers as well as replicating to replace themselves in the satellite cell pool

A

True

stem cell-like property

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16
Q

True or False

ANY injury to msucle cells will result in repair by satellite cells

A

true

myopathies
trauma
exercise

but other types of cells can participate in muscle regeneration

17
Q

What cells are also capable of generating new muscle?

A

Mesangioblasts
Pericytes
(both in the vessels)

bone marrow stem cells

AC133+ cell

muscle-derived stem cells

'’side population’’ cells

18
Q

Describe the features of mesoangioblasts

A

BV (large)assoicated stem cells from embryonic stage msucle

Able to differentiate into several types of mesodermal tissues such as smooth, cardiac, and skeletal muscle, bone and fat

Not thought to contribute greatly to normal muscle regeneration

possess great potential as therapeutic cell type

19
Q

Describe the features of Pericytes

A

BV (small) associated stem cells from post-natal stage muscle

located beneath the basal lamina of the small BVs

suitable for intravascular delivery

20
Q

Describe the features of AC133+

A

Blood-derived and skeletal muscle-derived populations that express the glycosylated epitope of human CD133 antigen

Make up 1% of the total mononucleated cells in human skeletal muscle regardless of age

Both blood and muscle derived populations can form myogenic cells

21
Q

Describe the features of bone marrow derived stem cells

A

circulating myogenic precursor cells have been described in the bone marrow

minimal contribution to muscle generation

22
Q

Describe the features of Muscle-derived stem cells (MDSC)

A

population of stem cells located in the muscle interstitial space and characterised as being positive for CD34 and SCA1

Demonstrated to regenerate skeletal muscle in a dystrophic mouse when delivered into the muscle or the vasculature

identified by a pre-plating technique from muscle biopsy samples

May represent a predecessor of the satellite cell

good myogoenic potential in vivo

23
Q

Describe the features ofSide population (SP) cells

A

population of stem cells identified by their unique ability to efflux the DNA-binding dye, hoechst

Located in both skeletal msucle and bone marrow

express Sca1 and do not express satellite cell markers (Pax7, Desmin)

Anatomically located outside of muscle fibers and are associated with the vasculature

haematopoietic potential in vitro

Myogenic potential when injected into regenerating muscle

24
Q

True or False

Other sources of stem cells may have a therapeutic benefit for treatment of disease

A

true

25
Q

What are the characteristics of the ideal stem cell to treat muscle wasting?

8 points.

A
  1. Be expandable in vitro without losing stem cell properties
  2. Be immuno-privileged (make sure they’re not recognised as foreign)
  3. be systematically-deliverable
  4. survive, proliferate and migrate upon arrival within host muscle
  5. differentiate into muscle fibers either to repair damaged fibers or replace lost fibers
  6. Reconstitute the satellite cell pool with functional stem cells
  7. Be capable of expressing required muscle genes once contributed to muscle
  8. Lead to improvement in muscle strength in order to improve patient quality of life
26
Q

Myoblast transplantation is the initial choice for cell therapy in skeletal muscle due to ..

A

ease of isolations

demonstrated good potential for therapy in mdx mouse

moved to clinical trials for DMD patients
- up to 10% dystrophin positive fibers in immunosupressed patients with multiple injections; hower

poor survival in vivo
limited migration from injection sites

unable to participate in long term regeneration

27
Q

Multiple studeis have demonstrated that satellite cell transplant result in muscle fiber formation and contribution to the satellite cell compartment

however, what are the issues with this?

A

satellite cells must be delivered directly to the muscle (cannot migrate)

poor contribution in the absence of a regenerating environment

exhibit poor survival in vivo (need to inject large numbers)

Multiple injections would be required for a therapeutic benefit

28
Q

What is a potential way of improving satellite cell transplantation?

A

Transplantation of myofibers and associated stem cells into injured muscle protects against age-related muscle degeneration in mice

29
Q

What are the advantages and disadvantages mesoangioblast transplants?

A

Advantages:

  • demonstrated to ameliorate dystrophy in the dog model of DMD
  • Can be delivered systemically

Disadvantages:
- Difficult to purify and relatively poorly defined cell population

30
Q

True or False

To date, no one cell type qualifies the criteria for a perfect therapeutic cell

A

true

many cell types are currently under investigation for use in muscle cell therapy

31
Q

Post-natal myogenesis follows a similar path to that of embryonic myogenesis, the main difference being the starting cell is a _____

A

satellite cell

muscle regeneration/repair is mediated by a population of resident adult stem cells termed satellite cells

32
Q

True or False

To date, no one cell type qualifies the criteria for a perfect therapeutic cell

A

true

many cell types are currently under investigation for use in muscle cell therapy

Muscle & Exercise Physiology (34 decks)

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