Adult Stem Cells

Question 1

Define what a stem cell is

Answer 1

• Can self-renew to give rise to more stem cells

- can differentiate into a range of more specialised cell types such as liver, lung and heart cells

Question 2

What are the different types of Stem cells?

Answer 2

Multipotent - most restricted, can form one type of cell (e.g. Haematopoetic stem cells can only form blood cells - but various types)
Pluripotent - can give rise to many cells - can give rise to an embryo (but not supportive tissue)
Totipotent - can give rise to the embryo, and the tissues that support its development such as the placenta

Question 3

What stages in embryonic development are the totipotent and pluripotent cells found?

Answer 3

• The fertilised egg is a totipotent cell until day 5
• Then you get the separation of the trophectoderm and the inner cell mass. The ICM is made of pluripotent stem cells that can give rise to the embryo and eventually the adult organism.

Question 4

What are multipotent stem cells and where are they found?

Answer 4

• They are adult stem cells
• Function as a repair system for the body, replenishing old and damaged tissues
• They are found in the brain (neural stem cells), heart (cardiac stem cells) and bone marrow (Haematopoeitic stem cells)

Question 5

What is the stem cell niche?

Answer 5

The microenvironment where stem cells are found - regulates stem cell activity
- Helps to regulate the balance between symmetric and asymmetric cell division

Question 6

What is the difference between asymmetric and symmetric division?

Answer 6

• Asymmetrical is when a stem cell divides into one stem cell and one differentiated cell. This maintains the stem cell pool in states of inactivity and quiescence
• Symmetrical is when a stem cell divides to give 2 stem cells, leading to the expansion of the stem cell pool - occurs due to injury/disease - in this state, stem cells are activated.

Question 7

What is the extracellular matrix?

Answer 7

a matrix that exists between cells

- it is the critical regulator of stem cell function

Question 8

Why can stem cells undergo more cell divisions than somatic cells?

Answer 8

The break down of telomeres is much slower in adult stem cells, and hardly occurs at all in pluripotent stem cells as they have an enzyme called telomerase which rebuilds the telomeres
- therefore they will not undergo DNA damage and stop dividing (senescence)

Question 9

Where are mesenchymal stem cells found?

Answer 9

Placenta
Umbilical blood
Adipose tissue
Adult muscle
Corneal stroma
Dental pulp

Question 10

What are mesenchymal stem cells?

Answer 10

Multipotent stem cells with the baility to differentiate into adipocytes, osteocytes, chondrocytes, muscle cells, stromal cells (connective tissue), fibroblasts (skin cells), and even neuron-like cells

Question 11

What is the therapeutic value of mesenchymal stem cells?

Answer 11

• They home to damaged tissue sites
• Have a high differentiation potential
• Produce trophic factors
• Immunomodulation

Question 12

What is osteogenesis imperfecta?

Answer 12

• Brittle bone disease
• A genetic disorder where osteoblasts produce defective type 1 collagen
• Symptoms include shortened stature, bony deformities, multiple fractures and osteopenia (reduced mineralisation and protein content of bone)

Question 13

What is ischemia?

Answer 13

Brain damage that occurs as a result of a region of the brain being starved of oxygen/nutrients due to a lack of blood supply

Question 14

How can Mesenchymal stem cells be used to treat ischemia in the brain?

Answer 14

• They activate microglia and modulate the anti-inflammatory response - inflammation can be detrimental to stimulation of neurogenesis and other repair processes
• They also produce growth factors to cause growth and differentiation of neural precursor cells, allowing them to mediate repair of the brain region.

Question 15

What are limbal stem cells?

Answer 15

The limbus is the narrow zone between the cornea and the bulbar conjunctiva
- corneal renewal and repair are mediated by stem cells from the limbus

Question 16

What is Transdifferentiation?

Answer 16

The process by which an adult cell can change from its initial differentiated state to another

• E.g. brain cells that transdifferentiate into blood cells, or bone to fat
• only been observed in vitro so far

Question 17

Give an example of transdifferentiation

Answer 17

Over expression of MyoD can differentiate Fibroblasts (skin) into muscle cells
ASCL = fibroblasts > neurons

Question 18

What is thought to be the reason for relapse after cancer therapies?

Answer 18

Cancer stem cells are resistant to therapies - relapse occurs because they can relocate and form a tumour in a different location.

Question 19

Which are the 4 ways we can target CSCs?

Answer 19

• Targeting surface markers
• Targeting the ABC binding casette
• Targeting the microenvironment
• Targeting signal cascades

Question 20

What is the problem with targeting surface markers on CSCs?

Answer 20

Not all CSCs express the markers, and some non-CSCs do - risk damaging healthy tissue

Question 21

What is the main signal cascade that we are targeting?

Answer 21

Mutations in the WNT pathway can lead to increased proliferation

Question 22

What is the Wnt signalling mechanism?

Answer 22

When WNT signalling is switched off, a degradation complex binds b-catenin and causes its ubiquitinilation and proteasomal degradation

• However when it is switched on, when Wnt ligands bind to their receptor (Frizzled), GSK3 is inhibited.
• This means that the degradation complex can no longer break down b-catenin, allowing it to enter the nucleus and switch on target gene expression
• mutations in any of this will cause aberrant cell differentiation and cancer