Lecture 29: Stem cells to the rescue? Flashcards
How many people die yearly from cardiovascular disease?
- 5million (31% of deaths)
- 4 million die of ischaemic heart disease
In Australia 43062
What are the current surgical treatment strategies for ischaemic heart disease?
Percutaneous coronary intervention (angioplasty and stenting)
Coronary artery bypass grafting
What are the current pharmacological interventions for ischaemic heart disease?
Anti-thrombotic
Beta-adrenergic antagonists
Calcium channel blockers
Nitrates
ACE inhibitors and ANGII receptor agonsists
Statins
What is the treatment strategy being designed now?
Cell-based interventions using stem cells
Which pluripotent stem cells are typically used for allogenic transplantation?
Embryonic stem cells
Which pluripotent stem cells are typically used for autologous transplantation?
Induced pluripotent stem cells
What are the pros and cons of using pluripotent stem cells?
Pros:
Unlimited proliferative potential
High cardiogenic potential
Cons:
Risk of tumor formation
Risk of arrhythmia
What are potential applications of pluripotent stem cells?
Cardiac repair and regeneration
Drug testing
Disease modelling
What are the pros and cons of using adult stem cells?
Pros:
Multipotent making tumor risk low
Autologous
Low immunologic rejection
Readily available
Cons:
Limited proliferative potential
Low cardiogenic potential
Risk of arrhythmia
Why are skeletal myoblasts a bad idea for heart transplantation?
Unable to electrically couple with host cardiomyocytes
How did bone-marrow derived cells perform during heart transplantation??
Meta-analysis indicated modest improvement in cardiac function
What is the benefit of using adipose mesenchyme derived stem cells?
They are very safe and easy to obtain.
What are the next generation stem cells?
Cardiac resident stem cells are isolated from heart tissue and are organ-specific stem cellsto treat organ-specific disease.
Cardiopoietic stem cells: These stem cells are derived from bone marrow stem cells which are transformed into heart cells via cardiogenic growth factors.
Where are W8B2+ cardiac stem cells derived from?
The Atrial Appendage
How are W8B2+ cardiac stem cells transformed into functional cardiomyocytes?
When stimulated by action potential
What other structures can cardiac stem cells get converted into?
Adipocytes
Osteocytes
Chondrocytes
What are the stages of infarct formation during ischaemia?
Inflammation: Cardiomyocyte death, infiltration of immune cells, and breakdown of ECM.
Proliferation: Proliferation of fibroblasts followed by angiogenesis, ECM production, and scar formation.
Remodelling: Heart hypertrophies and ventricular wall weakens
What is the direct effect of stem cells on the heart?
Some stem cells can differentiate directly into functional cardiomyocytes.
How do stem cells affect heart tissue indirectly?
via several paracrine effects
What are the paracrine effects following cell that act on the heart?
Proliferation of host cardiomyocytes
Attenuation of apoptosis
Modulation of matrix remodelling
Angiogenesis and vasculogenesis
Recruitment and activation of resident stem cells
What is the result of scar stabilization and increased capillary density?
Reverse remodelling (scar tissue is removed)
What is the effect of stem cell activation and new transplanted stem cells?
Cardiomyogenic rebuilding which improves contractile performance
How does cell therapy protect each stage of the cell cycle?
Inflammation: Prevent cardiomyocyte death
Attenuation of inflammation
Inihibition of ECM breakdown
Proliferation: Enhance angioggenesis, Proliferation CPC, decrease scar formation.
Remodelling: New contractile tissue are formed, and distention is decreased
What challenges are faced before stem cell transplantation?
Selection of patient source
Ideal cell type
Isolation methods (enzymatic or mechanical)
Cell expansion and culture conditions
Purification (for pluripotent stem cells)
