Muscle and Exercise Lecture 2.3 : Muscle Diseases - Stem Cell Therapies

Question 1

What are the three main classes of stem cells?

Answer 1

Embryonic, adult and inducible pluripotent cells
Allogenic - taken from one person, transplanted to another
Autologous - Taken from an individual, cultured, and replaced

Question 2

Do all tissue in the body have a stem cell population?

Answer 2

Yes, but some lose it early on, such as the heart.

Question 3

Stem cell transplant has been attempted. What is the only stem cell type transplanted with no problems ?

Answer 3

Bone marrow.

Question 4

Where are satellite cells found? How does this affect signalling?

Answer 4

Between the sarcolemma and basal lamina. Allows it to receive intra and extracellular signals.

Question 5

What are satellite cells when unused?

Answer 5

Quisecent.

Question 6

What is the division rate of satellite cells like when quiescent vs activated?

Answer 6

Very slow in quisecent state, very high when activated, only activated in response to injury.

Question 7

What state does the satellite cell exist in vs other stem cells (aerobic or anaerobic)?

Answer 7

Due to proximity to capillaries, is in the aerobic state, unlike other stem cells which are in an anaerobic state.

Question 8

What do satellite cells first upregulate?

Answer 8

Pax7

Question 9

What does Pax7 activate?

Answer 9

myoD.

Question 10

What does myoD upregulation do to a satellite cell?

Answer 10

Turns it into a myoblast, committed to the myogenic pathway.

Question 11

What do some satellite cells do shortly after activating myoD?

Answer 11

Turn off myoD to return to the quiescent state, and replenish base levels.

Question 12

What is the biochemical effect of myoD?

Answer 12

Downregulates Pax7, and upregulates myogenin.

Question 13

What happens when myogenin is upregulated?

Answer 13

Cells will no longer divide, and will fuse to form a fibre.

Question 14

Does a myoblast injection work?

Answer 14

No, myoblast cells don’t survive.

Question 15

Do cells that haven’t been cultured in vitro survive?

Answer 15

Yes, they do.

Question 16

Do cells with a myoD knockout survive?

Answer 16

Yes, 2-3 times more of them survive vs myoD positive cells.

Question 17

Why do cells with myoD or cells that have been cultured in vitro have such a small survival rate?

Answer 17

Commitment to the myogenic line causes the low survival rate. In vitro culturing increases myoD upregulation.

Question 18

Why are tomours so glycolytic?

Answer 18

Because glucose is needed to generate new building blocks.

Question 19

What do freshly isolated satellite cells rely on for energy?

Answer 19

Free fatty acids.

Question 20

What do satellite cells cultured in vitro rely on for energy?

Answer 20

Glycolysis.

Question 21

What are glycolytic genes for energy associated with?

Answer 21

Poor transplantation/survival rate.

Question 22

What happens to proliferation rate if you reduce glycolysis?

Answer 22

Increases.

Question 23

What happens to cells cultured in vitro? After several days?

Answer 23

Cells expressing Pax7 decrease quickly, and those with myoD upregulated increase quickly. After several days, most will be myoD+ and committed to the myogenic line, and transplant will fail.

Question 24

What does overexpression of TXNIP do to myoD?

Answer 24

Reduces myoD but is associated with senescence.