Lecture 29: Stem cells to the rescue? Flashcards Preview

Frontiers In Physiology > Lecture 29: Stem cells to the rescue? > Flashcards

Flashcards in Lecture 29: Stem cells to the rescue? Deck (27):
1

How many people die yearly from cardiovascular disease?

17.5million (31% of deaths)

7.4 million die of ischaemic heart disease

In Australia 43062

2

What are the current surgical treatment strategies for ischaemic heart disease?

Percutaneous coronary intervention (angioplasty and stenting)

Coronary artery bypass grafting

3

What are the current pharmacological interventions for ischaemic heart disease?

Anti-thrombotic

Beta-adrenergic antagonists

Calcium channel blockers

Nitrates

ACE inhibitors and ANGII receptor agonsists

Statins

4

What is the treatment strategy being designed now?

Cell-based interventions using stem cells

5

Which pluripotent stem cells are typically used for allogenic transplantation?

Embryonic stem cells

6

Which pluripotent stem cells are typically used for autologous transplantation?

Induced pluripotent stem cells

7

What are the pros and cons of using pluripotent stem cells?

Pros:

Unlimited proliferative potential

High cardiogenic potential

Cons:

Risk of tumor formation

Risk of arrhythmia

8

What are potential applications of pluripotent stem cells?

Cardiac repair and regeneration

Drug testing

Disease modelling

9

What are the pros and cons of using adult stem cells?

Pros:

Multipotent making tumor risk low

Autologous

Low immunologic rejection

Readily available

Cons:

Limited proliferative potential

Low cardiogenic potential

Risk of arrhythmia

10

Why are skeletal myoblasts a bad idea for heart transplantation?

Unable to electrically couple with host cardiomyocytes

11

How did bone-marrow derived cells perform during heart transplantation??

Meta-analysis indicated modest improvement in cardiac function

12

What is the benefit of using adipose mesenchyme derived stem cells?

They are very safe and easy to obtain.

13

What are the next generation stem cells?

Cardiac resident stem cells are isolated from heart tissue and are organ-specific stem cellsto treat organ-specific disease.

Cardiopoietic stem cells: These stem cells are derived from bone marrow stem cells which are transformed into heart cells via cardiogenic growth factors.

14

Where are W8B2+ cardiac stem cells derived from?

The Atrial Appendage

15

How are W8B2+ cardiac stem cells transformed into functional cardiomyocytes?

When stimulated by action potential

16

What other structures can cardiac stem cells get converted into?

Adipocytes

Osteocytes

Chondrocytes

17

What are the stages of infarct formation during ischaemia?

Inflammation: Cardiomyocyte death, infiltration of immune cells, and breakdown of ECM.

Proliferation: Proliferation of fibroblasts followed by angiogenesis, ECM production, and scar formation.

Remodelling: Heart hypertrophies and ventricular wall weakens

18

What is the direct effect of stem cells on the heart?

Some stem cells can differentiate directly into functional cardiomyocytes.

19

How do stem cells affect heart tissue indirectly?

via several paracrine effects

20

What are the paracrine effects following cell that act on the heart?

Proliferation of host cardiomyocytes

Attenuation of apoptosis

Modulation of matrix remodelling

Angiogenesis and vasculogenesis

Recruitment and activation of resident stem cells

21

What is the result of scar stabilization and increased capillary density?

Reverse remodelling (scar tissue is removed)

22

What is the effect of stem cell activation and new transplanted stem cells?

Cardiomyogenic rebuilding which improves contractile performance

23

How does cell therapy protect each stage of the cell cycle?

Inflammation: Prevent cardiomyocyte death
Attenuation of inflammation
Inihibition of ECM breakdown

Proliferation: Enhance angioggenesis, Proliferation CPC, decrease scar formation.

Remodelling: New contractile tissue are formed, and distention is decreased

24

What challenges are faced before stem cell transplantation?

Selection of patient source

Ideal cell type

Isolation methods (enzymatic or mechanical)

Cell expansion and culture conditions

Purification (for pluripotent stem cells)

25

Why is purification of stem cells important?

To ensure that all cells formed are the correct type of cells.

26

What challenges are faced during stem cell transplantation?

Dosing (getting the correct cell number)

Route of administration

Time of administration

27

What challenges are faced after stem cell transplantation?

cell survival

Cell retention and long-term engraftment

Differentiation into mature cardiomyocytes

Electrical integration and mechanical coupling

Decks in Frontiers In Physiology Class (35):