C8 Stem cells to the rescue

Question 1

1) Stem cell types: Pluripotent SC

Answer 1

• Embryonic (from blastocyst)
  
  • Can only be used allogenically (has to be derived from another source)
• Induced (using pluripotent transcription factors)
  
  • Can be used autologously (can use own cells for treatment)

Question 2

Pro/cons of pluripotent SC

Answer 2

• Pros:
  
  • Unlimited prolif potential
  • High cardiogenic potential
• Cons
  
  • Risk tumour formation
  • Risk arrhythmia

Question 3

Applications of pluripotent SC

Answer 3

• Cardiac repair and regeneration
• Drug testing
• Disease modelling

Question 4

2) Stem cell types: Adult SC (somactic SC)

Answer 4

• Undifferentiated
• Skeletal muscle, bone marrow, blood, fats, placenta/umbilical cord, heart

Question 5

Pros/cons of adult SC

Answer 5

• Pros:
  
  • Multipotent → low risk of tumour formation
  • Autologous
  • Low immunologic (low risk of rejection)
  • Readily available
• Consc:
  
  • Limited prolif potential
  • Low cardiogenic potential
  • Risk of arrhythmia

Question 6

List of 1st generation SC

Answer 6

1. Skeletal myoblast
2. Bone marrow-derived SC
3. Adipose-derived mesenchymal SC

Question 7

1st generation SC: 1) skeletal myoblast

Answer 7

• Undifferentiated
• Differentiated cells unable to electrically couple with host cardiomyocytes → causes arrythmias

Question 8

1st generation SC: 2) Bone marrow-derived SC

Answer 8

• Haemopoietic SC & endothelial progenitor cell
• Only shows modest improvement in heart function

Question 9

1st generation SC: 3) Adipose-derived mesenchymal SC

Answer 9

• Easily obtained, safe and feasible

Question 10

List of next generation SC

Answer 10

1. Cardiac resident SC
2. Cardiopoietic SC

Question 11

Next generation SC: 1) Cardiac resident SC

Answer 11

• (organ specific derived to treat organ-specific diseases)
• Isolated from heart tissue (invasive)
• Only c-Kit+ cells and Cardiosphere-derived cells went onto trials

Question 12

Next generation SC: 2) Cardiopoietic SC

Answer 12

• Cardiac lineage-specified bone marrow-derived mesenchymal cells
• Induce bone-marrow SC to cardiac SC

Question 13

W8B2 cardiac resident SC

Answer 13

• Have ability to turn into :
  
  • Cardiomyocytes
  • BV
  • Adipocytes
  • Osteocytes (bone)
  • Chondrocytes (cartilage)

Question 14

Stages of infarct healing following ischemia: 1) Inflammation

Answer 14

• Following cardiomyocytes death → breakdown ECM
  
  • SC: prevents apoptosis and ECM breakdown

Question 15

Stages of infarct healing following ischemia: 2) Proliferation

Answer 15

• Angiogenesis, ECM production
• Scar formation
  
  • SC: Enhance angiogenesis, ↓ fibrosis

Question 16

Stages of infarct healing following ischemia: 3) Remodelling

Answer 16

• Hypertrophy, weakening ventricular wall
• Compensate for loss of contraction
  
  • SC: Form new contractile tissues, ↓distention (stress)

Question 17

Direct SC therapy

Answer 17

• Differentiate into cells which are dead → Improves function of heart
• Problem: → may not integrate with host properly and cause arrhythmia

Question 18

Indirect SC therapy

Answer 18

• Release paracrine effects
  
  • Attenuate apoptosis
  • Secrete growth factors → modulate remodelling → ↓fibrosis
  • Promote angiogenesis → promote blood perfusion
  • Recruit resident SC → may turn into cardiac cell or promote the factors above

Question 19

What are the challenges to SC therapy

Answer 19

• Before transplantation
  
  • Selection of patient source (autologous/allogenic)
  • Preparing SC (expand, culture…)
• During transplantation
  
  • Cell number, dose, route, time → all affects the safety
• After transplantation
  
  • Cell survival, retention, ability to differentiate
  • Electrical integration, mechanical coupling