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Part 3 – PM3A > (PM3A) Stem Cells in Health & Disease > Flashcards

(PM3A) Stem Cells in Health & Disease Flashcards

1
Q

What is a stem cell?

A

Cells

Self-renew – can generate new cells

Differentiate into all cells of a particular lineage/ tissue

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2
Q

What are ESCs?

A

Embryonic stem cells

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3
Q

What is a fertilised egg called?

A

Zygote

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4
Q

What is a blastocyst?

A

Contains inner cell mass

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5
Q

Where is the inner cell mass found?

A

Blastocyst

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6
Q

What is the ICM?

A

Inner cell mass

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7
Q

Where are embryonic stem cells derived from?

A

Inner cell mass

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8
Q

What are the 3 germ layers?

A

(1) Ectoderm - outer part, e.g. nervous system
(2) Mesoderm - middle part, e.g. musculoskeletal system
(3) Endoderm - inner part, e.g. respiratory/ digestive systems

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9
Q

How is the potency of stem cells classified?

A

(1) Totipotent – give rise to any cell type
(2) Pluripotent – any cell of the body
(3) Multipotent – any cell of specific lineage/ tissue

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10
Q

What are neural stem cells?

A

Stem cells which give rise to cells of the nervous sytem

Multipotent - tissue-specific (adult)

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11
Q

What are hematopoietic stem cells?

A

Stem cells which give rise to cells of the nervous system

Multipotent - tissue-specific (adult)

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12
Q

What is cellular differentiation?

A

Cell goes from less specialised to a more specialised state

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13
Q

How can the differentiation of stem cells be driven in vitro?

A

(1) Developmental approach

(2) Empirical approach

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14
Q

What is an empirical approach, with regard to differentiation of stem cells in vitro?

A

Factors/ conditions that drive cells to differentiate to particular lineages

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15
Q

What is a developmental approach, with regard to differentiation of stem cells in vitro?

A

Knowledge that cells respond to extracellular cues/ cell-cell contact

Understanding of cell fates

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16
Q

What are progenitor cells?

A

Early descendants of stem cells

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17
Q

What is the intermediary molecule between B cells, T cells, NK cells, and dendritic cells from hematopoietic cells?

A

Lymphoid progenitor

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18
Q

What is the intermediary molecule between erythrocytes and platelets from hematopoetic cells?

A

Myeloid progenitor

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19
Q

Describe the potency of embryonic stem cells.

A

Pluripotent

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20
Q

What types of cell can be generated from pluripotent stem cells?

A

Any type of cell

Brain, liver, heart, blood etc

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21
Q

Name some sources of adult-derived (tissue-specific) stem cells.

A

Bone marrow

(1) Hematopoietic stem cells
(2) Mesanchymal stem cells

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22
Q

What do hematopoietic stem cells differentiate to?

A

Blood cells

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23
Q

What do mesenchymal stem cells differentiate to?

A

(1) Osteoblasts - bone
(2) Myocytes - muscle
(3) Adipocytes - fat
(4) Chondrocytes - cartilage

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24
Q

What are NSCs?

A

Neural stem cells

25
Q

What can neural stem cells differentiate to?

A

(1) Neurons
(2) Oligodendrocytes
(3) Astrocytes

26
Q

What is somatic cell nuclear transfer?

A

First method shown to reprogram adult cell to pluripotency

27
Q

How can we generate patient-specific stem cells?

A

Somatic cell nuclear transfer (SCNT)

(1) Transfer of nucleus from somatic cell to enucleated egg
(2) Generates a developing embryo via blastocysts

28
Q

How are embryonic stem cells generated via somatic cell nuclear transfer different from those generated in vitro?

A

Genetic code comes from donor somatic cell

Resulting cells have DNA from somatic cell (patient/ disease-specific)

29
Q

What are some of the ethical objections to the generation and use of embryonic stem cells?

A

(1) Usually derived from unused IVF embryos

(2) Destruction of viable embryo

30
Q

What are some technical limitations of embryonic stem cell use?

A

Cannot be made from individual patient

31
Q

Do ALL embryonic stem cells have ethical

complications?

A

Yes

32
Q

What types of pluripotent stem cells are there?

A

(1) Embryonic stem cells
(2) Somatic cell nuclear transfer
(3) Induced pluripotent stem cells (hiPSCs in humans)

33
Q

What is the benefit of induced pluripotent stem cells (iPSCs)?

A

No need to generate an embryo

34
Q

What are induced pluripotent stem cells?

A

Reprogrammed somatic cells directly into a stem cell

Using 4 transcription (Yamanaka) factors

35
Q

What are the four transcription factors used in induced pluripotent stem cells?

A

(1) Oct3/4
(2) c-Myc
(3) Klf4
(4) Sox2

36
Q

Which cell was first used for induced pluripotent stem cells (iPSCs)?

A

Mouse fibroblasts

37
Q

What are some benefits of iPSCs compared to embryonic stem cells (ESCs)?

A

(1) ESCs limited in availability
(2) ESCs limited in versatility
(3) Fewer ethical issues with iPSCs
(4) iPSCs give rise to possibility of personalised medicine
(5) Can be generated from any individual
(6) Carry genetics of individual gotten from
(7) Can use iPSCs to develop models of disease for regenerative medicine

38
Q

Which types of generated stem cells have risks of tumorigenicity?

A

Both ESCs and iPSCs

(1) Embryonic stem cells
(2) Induced pluripotent stem cells

39
Q

Where can multipotent stem cells be sourced?

A

(1) Pluripotent stem cells

(2) Adult stem cells in the body, e.g. bone marrow

40
Q

How can multipotent (adult) stem cells be used in developmental biology and basic research?

A

(1) Understanding disease + drug discovery

(2) Cell-based therapy

41
Q

How can stem cells be used in regenerative medicine?

A

(1) Bone marrow transplantation, HSCs (hematapoietic)
(2) Crohn’s disease
(3) Blindness
(4) Deafness
(5) Baldness
(6) Missing teeth
(7) Spinal chord injury

42
Q

What stem cells are being used in clinical trials?

A

(1) Hematopoietic stem cells – immunoablation for multiple sclerosis
(2) iPSCs – age-related macular degeneration (AMD), Parkinson’s, etc
(3) Embryonic stem cells – pancreatic beta cells for T1DM, ischaemia heart disease, macular degeneration
(4) Mesanchymal stem cells – for secretions of factors + immune modulation properties
(5) Neural stem cells – spinal chord injury, also for secretion of factors

43
Q

How can disease-specific/ patient-specific stem cells be generated?

A

From iPSCs

Induced pluripotent stem cells

44
Q

What types of stem cells are very difficult to acquire?

A

Neuron stem cells (NSCs)

From CNS

45
Q

What is a benefit of developing a disease-specific tissue compared to healthy tissue using human iPSCs?

A

Can identify differences between healthy + disease cells

Produce a phenotypic model

Can distinguish phenotypic differences

Identify events in disease progression

Test drugs for toxicity/ efficacy

Discovery of new drug targets

46
Q

Which disease mutations may cause Alzheimer’s disease?

A

(1) PSEN1
(2) PSEN2
(3) APP

47
Q

How can neural stem cells be generated?

A

From hiPSCs

Differentiated into different types of neurons/ astrocytes/ oligodendrocytes

48
Q

What are microglia?

A

Key cell of the brain

Immune system of the brain

Different lineage from neurons/ oligodendrocytes/ astrocytes

49
Q

How can be microglia be generated?

A

Derived from non-neural lineage

hiPSCs

50
Q

What is Alzheimer’s disease?

A

Neurodegenerative disorder

Can be familial/ sporadic

51
Q

What are some hallmarks of Alzheimer’s disease?

A

(1) Extracellular plaques of amyloid beta (Aß)

(2) Intracellular tangles of hyperphosphorylated Tau

52
Q

What is the amyloid hypothesis?

A

Accumulation of amyloid beta (Aß) peptide aggregates

53
Q

What is a potential benefit of hiPSCs in Alzheimer’s disease?

A

(1) Human models of Alzheimer’s in vitro

(2) Able to explore differences between familial + sporadic Alzheimer’s disease

54
Q

What is an isogenic control?

A

In modelling

A tissue with a disease which has had the mutation corrected

55
Q

What is fAD?

A

Familial Alzheimer’s disease

56
Q

What is sAD?

A

Sporadic Alzheimer’s disease

57
Q

What percentage of all Alzheimer’s disease cases does fAD account for?

A

~5%

58
Q

What percentage of all Alzheimer’s disease cases does sAD account for?

A

~95%

59
Q

What is a zygote?

A

Fertilised egg cell

Part 3 – PM3A (28 decks)

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