Lecture 16 - How To Mend A Broken Heart Flashcards
What %do cardiomyocytes make up of total number of cells in the heart
30% but make up 90% of the cells biomass
What are fibroblasts?
Contributes to making the skeleton and electrical conduction of the tissue
Smooth muscle blood cells have their own?
Vasaculture and provide the heart with its own blood supply
What does cardiac disease lead to a loss of?
Cardiomyocytes which leads to a decreased pumping function
What are ways in which you can lose myocytes?
Ischaemic heart disease, idiopathic cardiomyopathy, toxic - alcohol and anti cancer drugs
Are cardiomyocytes remodelling or regenerated?
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
Define heart failure
A clinical term when the heart cannot pump the blood around the body
What symptoms come with heart failure?
Breathless as you can’t oxygenate the blood as well, oedema, dizziness and tiredness
What happens to the heart during heart failure?
There is no cardiac regeneration, the heart appears to be unable to regenerate following the disease due scar tissue
How does the heart compensate for cell loss?
Through hypertrophy
Describe stem cell therapy for the heart
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
What is a characteristic of a stem cell?
Multipotent - normally isolated from bone marrow
What is the plasticity of stem cells?
They can change into other closely related cell types
Describe MSC transplantation to diseased hearts
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
Does MSC transplantation to diseased hearts work in humans?
Doesn’t seem to work as well
Why doesn’t MSC transplantation seem to work as well in humans?
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
How are the stem cells improving function?
Cardio-protective preventing the addition of loss cells, stimulation of endogenous regeneration, indirect contribution to Paracrine effects
What can c-kit Stem cells do?
Studies have shown that when you transplant c-kit into the heart they differentiate into muscle cells and increase and improve function
By the age of 25 what % of cardiomyocytes are made each year?
1%
Where do cardiomyocytes come from in the heart?
Stem cells contribute to the formation of cardiomyocytes - in the skin, brain and blood
What happens during the development of the heart and cardiomyocytes?
The heart grows, the cells grow and proliferate and make new cells. The cardiomyocytes divide to make new cells
What happens to the cardiomyocytes in zebra fish?
They divide to replace lost cardiomyocytes
What are two technologies that have been used to look at cardiomyocytes?
BrdU labelling and transgenic mice
Describe BrdU labelling
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
What happens to the analogue in BrdU labelling?
It is detected usually by an antibody labelling allowing cells that have undergone proliferation to be identified
What happens during normal ageing?
There is an increase in BrdU and this means that cardiomyocytes proliferate to replace lost cells and it doesn’t involve any stem cells
What happens to cardiac regeneration after ischaemic injury?
There is an increase in the number of unlabelled cardiomyocytes - after you have an injury stem cells differentiate into new cardiomyocytes
What does stem cell therapy do?
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
How do stem cells transplant work? - summary
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
What has been found out about C-kit cells?
Scientific fraud!!!
