Muscle and Exercise Lecture 2.3 : Muscle Diseases - Stem Cell Therapies Flashcards
What are the three main classes of stem cells?
Embryonic, adult and inducible pluripotent cells
Allogenic - taken from one person, transplanted to another
Autologous - Taken from an individual, cultured, and replaced
Do all tissue in the body have a stem cell population?
Yes, but some lose it early on, such as the heart.
Stem cell transplant has been attempted. What is the only stem cell type transplanted with no problems ?
Bone marrow.
Where are satellite cells found? How does this affect signalling?
Between the sarcolemma and basal lamina. Allows it to receive intra and extracellular signals.
What are satellite cells when unused?
Quisecent.
What is the division rate of satellite cells like when quiescent vs activated?
Very slow in quisecent state, very high when activated, only activated in response to injury.
What state does the satellite cell exist in vs other stem cells (aerobic or anaerobic)?
Due to proximity to capillaries, is in the aerobic state, unlike other stem cells which are in an anaerobic state.
What do satellite cells first upregulate?
Pax7
What does Pax7 activate?
myoD.
What does myoD upregulation do to a satellite cell?
Turns it into a myoblast, committed to the myogenic pathway.
What do some satellite cells do shortly after activating myoD?
Turn off myoD to return to the quiescent state, and replenish base levels.
What is the biochemical effect of myoD?
Downregulates Pax7, and upregulates myogenin.
What happens when myogenin is upregulated?
Cells will no longer divide, and will fuse to form a fibre.
Does a myoblast injection work?
No, myoblast cells don’t survive.
Do cells that haven’t been cultured in vitro survive?
Yes, they do.
Do cells with a myoD knockout survive?
Yes, 2-3 times more of them survive vs myoD positive cells.
Why do cells with myoD or cells that have been cultured in vitro have such a small survival rate?
Commitment to the myogenic line causes the low survival rate. In vitro culturing increases myoD upregulation.
Why are tomours so glycolytic?
Because glucose is needed to generate new building blocks.
What do freshly isolated satellite cells rely on for energy?
Free fatty acids.
What do satellite cells cultured in vitro rely on for energy?
Glycolysis.
What are glycolytic genes for energy associated with?
Poor transplantation/survival rate.
What happens to proliferation rate if you reduce glycolysis?
Increases.
What happens to cells cultured in vitro? After several days?
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.
What does overexpression of TXNIP do to myoD?
Reduces myoD but is associated with senescence.