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

Lecture 29: Stem cells to the rescue? Flashcards

1
Q

How many people die yearly from cardiovascular disease?

A
  1. 5million (31% of deaths)
  2. 4 million die of ischaemic heart disease

In Australia 43062

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2
Q

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

A

Percutaneous coronary intervention (angioplasty and stenting)

Coronary artery bypass grafting

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3
Q

What are the current pharmacological interventions for ischaemic heart disease?

A

Anti-thrombotic

Beta-adrenergic antagonists

Calcium channel blockers

Nitrates

ACE inhibitors and ANGII receptor agonsists

Statins

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4
Q

What is the treatment strategy being designed now?

A

Cell-based interventions using stem cells

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5
Q

Which pluripotent stem cells are typically used for allogenic transplantation?

A

Embryonic stem cells

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6
Q

Which pluripotent stem cells are typically used for autologous transplantation?

A

Induced pluripotent stem cells

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7
Q

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

A

Pros:

Unlimited proliferative potential

High cardiogenic potential

Cons:

Risk of tumor formation

Risk of arrhythmia

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8
Q

What are potential applications of pluripotent stem cells?

A

Cardiac repair and regeneration

Drug testing

Disease modelling

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9
Q

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

A

Pros:

Multipotent making tumor risk low

Autologous

Low immunologic rejection

Readily available

Cons:

Limited proliferative potential

Low cardiogenic potential

Risk of arrhythmia

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10
Q

Why are skeletal myoblasts a bad idea for heart transplantation?

A

Unable to electrically couple with host cardiomyocytes

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11
Q

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

A

Meta-analysis indicated modest improvement in cardiac function

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12
Q

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

A

They are very safe and easy to obtain.

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13
Q

What are the next generation stem cells?

A

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.

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14
Q

Where are W8B2+ cardiac stem cells derived from?

A

The Atrial Appendage

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15
Q

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

A

When stimulated by action potential

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16
Q

What other structures can cardiac stem cells get converted into?

A

Adipocytes

Osteocytes

Chondrocytes

17
Q

What are the stages of infarct formation during ischaemia?

A

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
Q

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

A

Some stem cells can differentiate directly into functional cardiomyocytes.

19
Q

How do stem cells affect heart tissue indirectly?

A

via several paracrine effects

20
Q

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

A

Proliferation of host cardiomyocytes

Attenuation of apoptosis

Modulation of matrix remodelling

Angiogenesis and vasculogenesis

Recruitment and activation of resident stem cells

21
Q

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

A

Reverse remodelling (scar tissue is removed)

22
Q

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

A

Cardiomyogenic rebuilding which improves contractile performance

23
Q

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

A

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
Q

What challenges are faced before stem cell transplantation?

A

Selection of patient source

Ideal cell type

Isolation methods (enzymatic or mechanical)

Cell expansion and culture conditions

Purification (for pluripotent stem cells)

25
Q

Why is purification of stem cells important?

A

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

26
Q

What challenges are faced during stem cell transplantation?

A

Dosing (getting the correct cell number)

Route of administration

Time of administration

27
Q

What challenges are faced after stem cell transplantation?

A

cell survival

Cell retention and long-term engraftment

Differentiation into mature cardiomyocytes

Electrical integration and mechanical coupling

Frontiers In Physiology (35 decks)

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