B 5.1 Generating and regenerating the heart Flashcards Preview

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Flashcards in B 5.1 Generating and regenerating the heart Deck (15)
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1

Heart development

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

2

The 2 'pools' of cardiac progenitor cells

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

3

Myocardial cell proliferation before birth

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

4

Features of M.I

  • 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

5

Features of heart failure

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

6

Regeneration of the damaged heart: Cell replacement

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

7

What is a stem cell

  • Capable of indefinite self-renewal & are undifferentiated

8

Embryonic stem cell differentiation

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

9

Where can toti/pluripotent SC be harvested from

  • Morula → toti cells
  • Inner cell mass → pluri

10

Features of adult stem cells

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

11

ESC vs ASC

12

How are ESC obtained?

  • 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

13

Adv/DAdv from different routes of SC adminstration

  • Intracoronary A route
  • Intraventricular inject

14

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

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

15

Tissue engineering as an alternative to SC injections

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