L8 - Stem Cells and the Future Flashcards

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1
Q

What are stem cells?

A

Cells that can differentiate into other types of cells and can divide to produce more of the same stem cells.

They are functionally unspecialised.

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2
Q

What was the early dogma on neurogenesis?

A

Once early childhood was reached, the number of neurons in the brain only decreases.

Idea that the central nerve system just doesn’t regenerate at all.

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3
Q

What forms of neural replacement occurs aside from neurogenesis?

A

Synapses are very dynamic systems that repeatedly appear and disappear, as they are replaced and regenerate.

Scaffolding proteins that form large molecular complexes in synapses have a very high rate of turnover and are highly mobile.

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4
Q

What are the timescales of turnover of synapses?

A

Minutes/hours, whole synapse taking in the order of months to replace.

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5
Q

What are the timescales that it takes spines to turnover?

A

Hours, the whole structure taking in the order of months/years to fully replace.

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6
Q

What is neurogenesis?

A

The growth and development of nervous tissue

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7
Q

In most regions of the brain, new neurons are not produced once you are born. What are the exceptions, and why?

A

New neurons are made throughout life in the olfactory bulb (OB), and dentate gyrus (DG) of the hippocampus.

This is likely because olfactory stimuli are constantly stressing the cells, so a mechanism is developed to replace them.
In the DG/hippocampus it is thought to be related to the acquisition of new memories.

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8
Q

What did Spalding et al., (2013) find about the regrowth of neurons in the hippocampus using radioactive elements?

A

In the 1950s, nuclear bomb testing began, causing the levels of radioactive Carbon 14 (14C) to increase.

Presence of 14C in a neuron would indicate that it had been created since nuclear testing began.

Found that 1/3 of hippocampal cells are in a renewing state - estimated that an adult creates 700 new neurons per day (2% of annual turnover rate)

Indicates neurogenesis in adults.

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9
Q

What are the two types of stem cells, and what are the differences?

A

Adult stem cells - organ-specific and are restricted in their developmental potential (i.e. can only be new nerve cells, or skeletal muscle cells)

Embryonic stem cells - appear unrestricted in their developmental potential

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10
Q

What is self-renewal?

A

The ability to go through numerous cycles of cell division while maintaining the undifferentiated state.

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11
Q

What is potency?

A

The capacity to differentiate into specialised cell types - to be able o give rise to any mature cell type.

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12
Q

What are the 5 levels of potency?

A
Totipotent (/omnipotent)
Pluripotent
Multipotent
Oligopotent
Unipotent
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13
Q

What are totipotent (/omnipotent) stem cells?

A

Stem cells which can construct a complete, viable organism. Found/produced when a sperm and egg fuse.

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14
Q

What are pluripotent stem cells?

A

Descendants of totipotent cells, and can differentiate into nearly all cells.

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15
Q

What are multipotent stem cells?

A

Can differentiate into a number of cell types, but only those of a closely related family of cells.

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16
Q

What are oligopotent stem cells?

A

Can differentiate into only a few cell types, such as lymphoid or myeloid (bone marrow) stem cells.

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17
Q

What are unipotent stem cells?

A

Can produce only one cell type, their own - they have the property of self-renewal.

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18
Q

What are progenitor cells?

A

Can differentiate into a specific type of cell, but is more specific than a stem cell and can only differentiate into its target cell. Cannot self-replicate/perform self-renewal like a stem cell can.

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19
Q

Embyronic stem cells are usually what level of potency?

A

Pluripotent or toti/omnipotent

20
Q

What does iPS stand for?

A

Induced pluripotent cells

21
Q

What are iPS’?

A

Pluripotent stem cells which are artificially created in the lab by reprogramming a patient’s own cells.

22
Q

What can iPS cells be made from?

A

Readily available cells including fat, skin and fibroblasts (cells that produce connective tissue)

23
Q

What is the potential of iPS cells for therapy?

A

High:

  • mouse iPS cells can become any cell in the body, or even form into an entire mouse
  • the same appears to be true for human iPS cells.
  • no danger of rejection
24
Q

What is therapeutic cloning?

A

A method for creating patient-specific embryonic stem (ES) cells.

Nucleus of a patient’s cell is injected into a recipients’ egg. The egg cell then develops and divides, ES cells can be extracted. Can be inserted back into patient without being rejected.

25
Q

What is disease modelling?

A

Using stem cells carrying the disease gene (or engineered to), researchers are able to model disease processes in vitro, leading to greater understanding of the mechanisms underlying the disease.

26
Q

What is drug toxicity screening/drug discovery?

A

Tissue grown from stem cells will react to drugs in the same way that real human tissue will, so scientists can test the effectiveness/toxicity of new drugs.

27
Q

What is gene therapy?

A

Uses induced stem cells from the patients’ body to introduce a new copy of a gene to correct a genetic fault.

28
Q

What is cell replacement therapy?

A

Attempts to replace an entire tissue, that has been lost or damaged as a result of neurological diseases.

29
Q

What are olfactory ensheathing cells?

A

Type of macroglia in the nervous system which enclose non-myelinated axons of olfactory neurons.

They have been tested successfully in axonal regeneration in adult rats with spinal cord damage.

30
Q

What does OEC stand for?

A

Olfactory ensheathing cells

31
Q

What are the extra problems with spinal cord injuries?

A
  • Damage to the spinal cord cuts neurons but also causes fluid filled cysts to form a barrier, which prevents nerve regrowth across the injury site.
  • Spinal cord cells react to injury by producing chemicals which act as ‘stop growth’ signals, further preventing nerve regrowth.
32
Q

What is the solution to the extra problems caused by spinal cord injuries?

A

Implantation of scaffolds, which can provide mechanical support and physical guidance for axon regrowth. Also seems to address/interfere with the chemical imbalance.

33
Q

What is PEG, and what does it do?

A

Polyethene glycol.

Reduces volume of cysts - less physical barrier.

Encourages external growth from one side to another.

34
Q

What seems to be the best way to bridge the gap across a spinal cord injury?

A

A combination of PEG and stem cells.

35
Q

What is a simple way to bridge the gap, and restore nerve damage?

A

Simply laying down nerves from somewhere else in the body encourages growth of new nerves in the location of the break.

36
Q

What are the two ways to use stem cell-derived neurons for grafting in PD?

A

Using dopamine neurons from:

  • growth of Da from ES cells from a blastocyst (hollow ball of differentiating cells)
  • extraction from the ventral area of an aborted foetus’ midbrain (area where dopamine neurons originate)

–> Da injected into the striatum of the PD patient

37
Q

Describe the clinical effectiveness of the two ways stem cell-derived neurons used for grafting in PD treatment.

A
  • fetal DA cell replacement therapy has showed variable, but mostly negative results. Development of dyskinesia’s occur.
  • ES cell transplants. Establishes neurons which can produce dopamine indefinitely.
38
Q

Overall, why is it problematic to treat PD?

A
  • PD is not a homogenous disorder, and so one type of stem cell treatment is not going to be effective in all cases - patients present with different cognitive profiles and disease courses.
  • some signs of PD can take over the grafted neurons a decade after surgery
  • remains unknown whether it is more effective to inject Da into target (striatum) or source (SNc)
39
Q

Why is it easier to treat HD than PD?

A

HD is caused by a single inherited gene.

- genetic tests allow diagnostic certainty

40
Q

What are the principles of cell replacement in HD?

A
  • developing medium spiny neurons from embryonic striatum

- placing them back directly to the area of degeneration

41
Q

What happened to the first 5 patients who had grafts?

A
  • 2 had grafts which did not survive

- 3 grafts survived, leading to a clear sustained improvement in some modalities/

42
Q

What is MS?

A

Multiple sclerosis - autoimmune disease which causes a loss of myelin sheath around axons. Stops axons working properly - signalling is ineffective.

43
Q

What does HSCT stand for and what is it?

A

Haematopoietic stem cell transplantation

Stem cells that can produce all cells in blood, including immune cells

44
Q

What are the therapies involving stem cells being used to treat MS?

A

HSCT, which resets the immune system by inserting stem cells to replace lost immune cells in the blood.

Chemotherapy removes harmful immune cells, and then bone marrow stem cells are used to rebuild the immune system.

45
Q

What is the example of limb generation in mammals?

A

Lizards and newts can re-grow tails.

Axelotls and fetuses can regrow entire limbs.