B 5.1 Generating and regenerating the heart

Question 1

Heart development

Answer 1

• Cardiac myocytes are derived from mesoderms
• Comes from looping of tube & fusing
• Transcription factors guide cardiac development

Question 2

The 2 ‘pools’ of cardiac progenitor cells

Answer 2

• Primary heart field (cardiac crescent,LV, A)
• Secondary heart field (RV, outflow tract)

Question 3

Myocardial cell proliferation before birth

Answer 3

• Cardiomyocytes exit cell cycle at birth - central dogma
• Cell # determined at birth
  
  • Then controlled by apoptosis & differentiation
• Myocyte turnover rate ~1% throughout life

Question 4

Features of M.I

Answer 4

• Sudden
• 70-90% due to plague rupture & thrombus formation
• Prolonged ischemia → necrosis
  
  • Dead myocardium is replaced with connective tissues → ↓ function
• LV has 2-4billion cardiomyocytes
  
  • MI kills 25% in a few hours
• The heart generates minimal new cardial muscle cells

Question 5

Features of heart failure

Answer 5

• Progressive
• Ventricular pump failure
• Causes include cardiac hypertrophy & MI (Etiology unknown)
• Myocyte loss > replacement

Question 6

Regeneration of the damaged heart: Cell replacement

Answer 6

• Differentiated cells (skeletal myoblasts) transplant in damaged myocardium
  
  • Initial results from clinical trials → ↑ejection fraction
• BUT risk of arrhythmia

Question 7

What is a stem cell

Answer 7

• Capable of indefinite self-renewal & are undifferentiated

Question 8

Embryonic stem cell differentiation

Answer 8

• Toti → pluri → multi → somatic (becomes more specialised)

Question 9

Where can toti/pluripotent SC be harvested from

Answer 9

• Morula → toti cells
• Inner cell mass → pluri

Question 10

Features of adult stem cells

Answer 10

• Undergo renewal & repair
• Potential autologous (self-derived) → source for tissue regen
• Bone marrow has hematopoietic & mesenchymal SC

Question 11

ESC vs ASC

Answer 11

Question 12

How are ESC obtained?

Answer 12

• Therapeutic cloning → grown in vitro → destroy embryo (ethical significance)
• Nuclear reprogramming:
  
  • Skin cell harvest → genes induced reprogramming → pushes cells back to pluripotency
  • Cells not as potent as real ESC

Question 13

Adv/DAdv from different routes of SC adminstration

Answer 13

• Intracoronary A route
• Intraventricular inject

Question 14

What can be seen after injecting cardiac progenitor cells in rats post MI

Answer 14

• SC isolated from 2yo mice → cells expressed cardiogenic transcription factors → comitted to myocyte lineage
• Injected into post MI hearts → formed new myocardium → ↑ cardiac function

Question 15

Tissue engineering as an alternative to SC injections

Answer 15

• Growing heart muscles → complete replacement of diseased myocardium
• But may interrupt flow of electrical conduction patterns