Lecture 11

Question 1

immature VS adult cardiomyocyte

Answer 1

immature cell has a way less sophisticated structure : no connection between the cells, more rounded, only a few sarcomeres and a small sarcoplasmic reticulum

Question 2

heart development : early fetal stage, late fetal stage, neonatal stage, adult stage

Answer 2

1) heart tube, trabeculations start being formed, to increase surface area

2) chamber formation, specification of cardiac conducting cells (purkinje fibers)

3) hypertrophic growth, heart grows to meet work load demand

4) fully mature, left ventricle is thicker.

Question 3

in which of the 4 development stages can the cardiomyocytes proliferate more ?

Answer 3

In the first two stages.
Then it becomes complicated. They can then only increase in size.

Question 4

two types of myocardial infarction

Answer 4

type 1 : with coronary obstruction

type 2 : due to lacking oxygen without a coronoary obstruction (ex : anemia)

Question 5

explain the myocardial infarct progression. What is the border zone ?

Answer 5

1) necrotic : protein denaturation, membrane break down
2) granulation tissue : fibroblasts, pro-collagen
3) scar : fibroblasts, collagen I
-> non-contractile region of heart. The rest tries to compensate.

border zone : cells close to the infarct are not perfused enough and go into hibernation until they die -> progression of damage

Question 6

what is the cardioyocyte turnover in humans ?

Answer 6

less than 50% are exchanged during a normal lifespan.

The renew decreases from 1% annually at 20 to 0.3% at 75.

Question 7

how does the cardiac regeneration work in zebrafish ?

Answer 7

cells around injury de-differentiate and re-enter the cell cycle -> division -> differentiation and maturation

Question 8

how long do mammals have the capability to regenerate the cadiomyocytes ?

Answer 8

until 5 days post birth. After that, there is scar tissue and loss of function.

Question 9

3 strategies to improve cardiac regeneration in vivo

Answer 9

1) cardioprotection (control inflammatory processes)

2) heart regeneration (dedifferentiation)

3) heart repair (reprogramming stem cells)

Question 10

what kind of cardiac patches could be used ?

Answer 10

• partial reconstruction
• transmural repair
• active global support
• paracrine support (GF)
• cardiac restraint (avoid overgrowth)

Question 11

what is hard about in vitro cardiomyocytes ?

Answer 11

Very difficult to have a mature cardiomyocyte in vitro.

Question 12

2 things needed in a biomimetic approach

Answer 12

oxygen supply

physical forces : electrical, mechanical, excitation - contraction coupling

Question 13

5 kinds of mechanical stimulation. The two most used for cardiac ?

Answer 13

• auxotonic (isometric, isotonic)
• static stretch : isometric
• cyclic stretch
• torsion
• hydrodynamic shear stress

auxotonic (passive force) and isotonic (active force)

Question 14

advantage of mesoscale ? new bioreactor design ?

Answer 14

auxotonic AND isotonic AND electrical

we can have a rigid + flexible wire for auxotonic, a moving wire for isotonic, and the wires are connected to electrodes for electrical

Question 15

how is current generated in our body ?

Answer 15

ions dissolving in water (and not electrons moving)

Question 16

in vivo oxygen supply : two ways to vascularize the graft

Answer 16

1) in vitro pre-vascularization : microfluidic channels, cell coculture

2) in vivo vascularization : genetically modified cells that express safe VEGF levels