Lecture 16 - How To Mend A Broken Heart

Question 1

What %do cardiomyocytes make up of total number of cells in the heart

Answer 1

30% but make up 90% of the cells biomass

Question 2

What are fibroblasts?

Answer 2

Contributes to making the skeleton and electrical conduction of the tissue

Question 3

Smooth muscle blood cells have their own?

Answer 3

Vasaculture and provide the heart with its own blood supply

Question 4

What does cardiac disease lead to a loss of?

Answer 4

Cardiomyocytes which leads to a decreased pumping function

Question 5

What are ways in which you can lose myocytes?

Answer 5

Ischaemic heart disease, idiopathic cardiomyopathy, toxic - alcohol and anti cancer drugs

Question 6

Are cardiomyocytes remodelling or regenerated?

Answer 6

They are remodelling, they become bigger to help with the loss. It is not good long term as there is a loss of blood being able to pump around the body

Question 7

Define heart failure

Answer 7

A clinical term when the heart cannot pump the blood around the body

Question 8

What symptoms come with heart failure?

Answer 8

Breathless as you can’t oxygenate the blood as well, oedema, dizziness and tiredness

Question 9

What happens to the heart during heart failure?

Answer 9

There is no cardiac regeneration, the heart appears to be unable to regenerate following the disease due scar tissue

Question 10

How does the heart compensate for cell loss?

Answer 10

Through hypertrophy

Question 11

Describe stem cell therapy for the heart

Answer 11

Mesenchymal stem cells used, (immune privileged) it maybe be possible that you can take stem cells from one individual and put them in another individual without initiating an immune response

Question 12

What is a characteristic of a stem cell?

Answer 12

Multipotent - normally isolated from bone marrow

Question 13

What is the plasticity of stem cells?

Answer 13

They can change into other closely related cell types

Question 14

Describe MSC transplantation to diseased hearts

Answer 14

Reduced scar tissue, improved pumping function, improved heart structure and a longer life - it seems to work in animal studies when rats had a heart attack

Question 15

Does MSC transplantation to diseased hearts work in humans?

Answer 15

Doesn’t seem to work as well

Question 16

Why doesn’t MSC transplantation seem to work as well in humans?

Answer 16

A small number of MSCs go into the myocardium and ever fewer differentiate into cardiomyocytes. There is no evidence that heart gets better and no evidence that the stem cells have become cardiomyocytes

Question 17

How are the stem cells improving function?

Answer 17

Cardio-protective preventing the addition of loss cells, stimulation of endogenous regeneration, indirect contribution to Paracrine effects

Question 18

What can c-kit Stem cells do?

Answer 18

Studies have shown that when you transplant c-kit into the heart they differentiate into muscle cells and increase and improve function

Question 19

By the age of 25 what % of cardiomyocytes are made each year?

Answer 19

1%

Question 20

Where do cardiomyocytes come from in the heart?

Answer 20

Stem cells contribute to the formation of cardiomyocytes - in the skin, brain and blood

Question 21

What happens during the development of the heart and cardiomyocytes?

Answer 21

The heart grows, the cells grow and proliferate and make new cells. The cardiomyocytes divide to make new cells

Question 22

What happens to the cardiomyocytes in zebra fish?

Answer 22

They divide to replace lost cardiomyocytes

Question 23

What are two technologies that have been used to look at cardiomyocytes?

Answer 23

BrdU labelling and transgenic mice

Question 24

Describe BrdU labelling

Answer 24

It is a way to detect cell division, by the identification of DNA replicating bromodeoxyuridine. During DNA synthesis as the new leading strand is being synthesised the analogue is incorporated into the DNA instead of thymine

Question 25

What happens to the analogue in BrdU labelling?

Answer 25

It is detected usually by an antibody labelling allowing cells that have undergone proliferation to be identified

Question 26

What happens during normal ageing?

Answer 26

There is an increase in BrdU and this means that cardiomyocytes proliferate to replace lost cells and it doesn’t involve any stem cells

Question 27

What happens to cardiac regeneration after ischaemic injury?

Answer 27

There is an increase in the number of unlabelled cardiomyocytes - after you have an injury stem cells differentiate into new cardiomyocytes

Question 28

What does stem cell therapy do?

Answer 28

Increased contribution of stem cell to the cardiomyocyte population. These cells have to be derived from the hearts of the injured animal as they have expressed GFP. Increase in the number of non labelled cardiomyocytes. Transplant of the stem cells enhances the cardiomyocytes

Question 29

How do stem cells transplant work? - summary

Answer 29

Doesn’t work as expected, they don’t differentiate into new cardiomyocytes they produce paracrines that promote proliferation of mature cardiomyocytes and also promote the differentiation of an existing stem cell to make new cardiomyocytes

Question 30

What has been found out about C-kit cells?

Answer 30

Scientific fraud!!!