Cardio 8

Question 1

How many deaths did CVD cause in 2012 and how many of these were due to ischemic heart disease?

Answer 1

17. 5 million

7. 4 million

Question 2

How many deaths due to CVD in Aus in 2013, and how many due to ischemic heart disease?

Answer 2

43,603 deaths due to heart disease in 2013, with 20,000 of these due to ischemic heart disease

Question 3

What are the surgical treatments for ischemic heart disease?

Answer 3

• Percutaneous coronary intervention – angioplasty and stenting
• Coronary artery bypass grafting

Question 4

What are the pharmacological treatments for ischemic heart disease?

Answer 4

• Anti-thrombotic
• Beta adrenergic antagonists (lower BP)
• Calcium channel blockers
• Nitrates (if suffering from angina)
• ACE inhibitors
• Statins (lower cholesterol)

Question 5

What are embryonic stem cells?

Answer 5

Derived from preimplantation embryo (blastocyst), first human line by Thomson in 1998, allogenic transplantation (cannot use own stem cells, must be derived from another source), pluripotent

Question 6

What are induced pluripotent stem cells?

Answer 6

Reprogrammed from somatic cells with pluripotent transcription factors, discovered by Takahashi in 2006, autologous transplantation

Question 7

What are the pros and cons of pluripotent stem cells?

Answer 7

Pros: unlimited proliferative potential, high cardiogenic potential
Cons: risk of tumour formation, risk of arrhythmia

Question 8

What are the pros and cons of adult stem cells?

Answer 8

Pros: multipotent (low risk of tumour formation), autologous, low immunologic potential, readily available
Cons: limited proliferative potential, low cardiogenic potential, risk of arrhythmia

Question 9

What adult stem cell is most commonly used for treatment?

Answer 9

Bone marrow

Question 10

What are the first generation stem cells?

Answer 10

Skeletal myoblasts, bone marrow derived and adipose derived

Question 11

What are the features of skeletal myoblasts?

Answer 11

Undifferentiated cells residing in the muscular tissue, first cell type tested in patients, differentiated cells are unable to electrically couple with host cardiomyocytes (arrhythmia)

Question 12

What are the features of bone marrow derived SC?

Answer 12

Unfractioned mononuclear cells, mesenchymal cells or CD34 cells, provided modest improvement in cardiac function

Question 13

What are the features of adipose derived mesenchymal stem cells?

Answer 13

Multipotent stem cells from fat tissue, easily obtained via liposuction aspirates, safe and feasible

Question 14

What are the next generation stem cells?

Answer 14

Cardiac Resident Stem Cells, cardiopoietic stem cells

Question 15

What are the features of cardiac resident stem cells?

Answer 15

Isolated from heart tissue, organ specific stem cells to treat organ specific disease, only c-Kit and cardiosphere cells have been trialled and shown promising results

Question 16

What are the features of W9B2+?

Answer 16

Found in cell surface membrane, ability to turn into heart cells (cardiomyocyte) and can show AP when stimulated with current. Can also turn into blood vessels, osteocytes (bone), chondrocytes (Cartilage) and adipocytes. Can differentiate into a select group of structures (need specific drug cocktail to determine what structure they turn into - not spontaneous

Question 17

What are the features of cardiopoietic stem cells?

Answer 17

Not naturally isolated from stem cell - can be invasive to isolate stem cells direct from the heart, take advantage of more readily available stem cell (bone marrow) and treat them with factors to turn them into cardiac stem cells for transplant

Question 18

What happens during inflammation after an ischemic insult?

Answer 18

• Inflammation
• Cardiomyocyte death
• Immune cell infiltration - ECM breakdown
• Heart may rupture
• 1 week

Question 19

What happens during proliferation after an ischemic insult?

Answer 19

• Fibroblasts - form scar tissue
• Growth factors are secreted and cause angiogenesis
• 1-2 weeks

Question 20

What happens during remodelling after an ischemic insult?

Answer 20

• Scar (limited heart cells)
• Weak wall
• Heart cells hypertrophy to compensate for loss of contraction

Question 21

What is the mechanism of action of cell therapy?

Answer 21

• Secrete growth factors for angiogenesis (increase reperfusion) and compensation for cell death
• Remodel scar tissue and reduce fibrosis
• Activate resonant stem cells in the heart (more heart cells or more growth factors)

Question 22

What are the challenges with cell therapy?

Answer 22

• No ideal cell source – no perfect stem cell
• Young, healthy patients are ideal candidates for stem cell donation
• Purification of cells is required to minimise risk of cancer formation
• Choice of admin affects safety, how well the stem cells remain and distribute in the target tissue