Lecture 1: Generating & Regenerating The Heart

Question 1

How many cells in the blastocyst, and what does the inner cell mass become?

Answer 1

16-32 cells

Endoderm, mesoderm, ectoderm

Question 2

What does the trophoblast go on to develop?

Answer 2

Extra embryonic tissues and membranes - placenta

Question 3

What does the ectoderm make?

Answer 3

Skin, brain, eyes

Question 4

What does the mesoderm make?

Answer 4

Bone, blood, muscle

Question 5

What does the endoderm make?

Answer 5

Lung, liver, gut lining

Question 6

Where are cardiac myocytes derived from?

Answer 6

Mesoderm

Question 7

What is the pattern of heart development?

Answer 7

Day 15: heart is a crescent
Day 21: heart is a linear tube
Day 28: Heart loops to make right and left sides
Day 50: remodelling of the heart

Question 8

What is in the primary heart field?

Answer 8

Cardiac crescent, left ventricle, atria

Question 9

What is in the secondary heart field?

Answer 9

Right ventricle and outflow tract

Question 10

When do hyperplasia and hypertrophy occur?

Answer 10

Hyperplasia occurs before birth and for the first few months of life and hypertrophy occurs from then on

Question 11

What is the classic dogma?

Answer 11

Cardiomyocytes exit cell cycle at birth and cell number in adult heart is largely determined at birth

Question 12

What is the myocyte turnover per year?

Answer 12

1%

Question 13

Why does MI occur?

Answer 13

Rupture of fatty atherosclerotic plaque in a blood vessels which travels through and causes a clot downstream - blood flow obstructer - ischemia

Question 14

What is 70-90% of MI due to?

Answer 14

Plaque rupture and thrombus formation

Question 15

What replaces dead myocardium after MI and what does this mean?

Answer 15

Connective tissue leading to reduced cardiac function

Question 16

How many cardiomyocytes are in the heart and how many can an MI kill?

Answer 16

2-4 billion, 25%

Question 17

What is heart failure?

Answer 17

Inability of the heart to pump efficiently to meet demand

Question 18

What were the benefits and disadvantages of using skeletal myoblasts for cell replacement therapy?

Answer 18

Increased ejection fraction but significant risk of arrhythmia (skeletal cells don’t contract as one)

Question 19

What is a stem cell?

Answer 19

A cell capable of indefinite renewal that is undifferentiated

Question 20

What is the source of pluripotent stem cells and what is the consequence?

Answer 20

ICM (blastocyst)

Destroy embryo

Question 21

What is the source of multipoint stem cells?

Answer 21

Bone marrow

Question 22

What is the source of induced pluripotent stem cells?

Answer 22

Skin cells

Question 23

What is therapeutic cloning?

Answer 23

Take a cell from general body, remove nucleus and put it in an egg cell - induced to form embryo

Question 24

What is nuclear reprogramming?

Answer 24

Apply factors to reprogram cells - back to multipoint form

Question 25

What are the advantages and disadvantages of intracoronary stem cell admin to the heart?

Answer 25

Advantages: cells travel to regions where nutrient and oxygen supply is preserved

Disadvantage: homing of stem cells requires migration out of the vessel to the muscle (low efficiency)

Question 26

What are the advantages and disadvantages of intraventricular stem cell admin to the heart?

Answer 26

Advantages: not limited by cell uptake of embolic risk, direct to site

Disadvantages: risk of ventricular perforation and cell death

Question 27

What happened when stem cells were used as treatment for MI?

Answer 27

Trials were safe, EF increased initially but there were no major long term differences

Question 28

What are the 3 main types of cells derived from the embryo?

Answer 28

Embryonic stem cells, trophoblast stem cells, primordial germ cells