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SCRA > 14. regenerative biology 4 > Flashcards

14. regenerative biology 4 Flashcards

1
Q

what things can cause damage and disease in the lungs? (6)

A
  • bacteria/viral infection
  • inflammation
  • allergy
  • asthma
  • physical trauma
  • cancer
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2
Q

what does asbestos cause?

A

a specific type of lung cancer

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3
Q

what is idiopathic fibrosis?

A

when the lung starts laying down fibrous scars tissue - don’t know why this happens but affects lung function

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4
Q

how many people worldwide suffer from chronic obstructive pulmonary disease (COPD) and how many people die? and how does it affect people?

A

210m
3m/year
>reduces quality of life and requires expensive medication - these only address symptoms

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5
Q

what happens to the lung in COPD?

A

irreversible apoptosis of epithelium

proteolysis of alveoli and ECM

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6
Q

why is regenerative medicine of the lung important? (4)

A

> there are too few donors
transplants are risky and expensive
don’t always work
immunosuppressant

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7
Q

many different regions – many different local environments, each with different blood and oxygen supply in the lung. how many cell types are there in the lungs?

A

40

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8
Q

what does the dramatic mechanistic properties of the lungs impacts?

A

the cell biology of lung cells

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9
Q

all the different regions are affected by disease and damage differently, TRUE or FLASE

A

true

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10
Q

what is the normal response of the lungs to chronic/acute injury? (5)

A
  1. macrophages and neutrophils activated
  2. secret GF, cytokines, IL
  3. other immune cells recruited
  4. nearby epithelial cells and fibroblasts secrete ECM and/or divide
  5. these secrete MMPs, reorganise cytoskeleton and migrate to close the wound
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11
Q

how does the immune response affect regernation in the lungs?

A

some aspects of this help regenerate lungs but other hinder it, the balance needs to be go right

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12
Q

what is fibrosis? and what do we want to do about this?

A

scarring response which we want to minimise without risking patients survival

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13
Q

what happens when the injury response is over?

A
  • cell stop dividing
  • immune cells go away
  • macrophages return to resting
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14
Q

what can also occur to allow tissue remodelling?

A

apoptosis

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15
Q

what will 3D development of lungs in a dish allow us to learn more about? and what could we also do?

A

how the cocktail of growth factors, interleukins and cytokines are involved in the healing process
>we could injure them and model COPD

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16
Q

people have been hunting for endogenous lung stem cells, what did a recent review suggest?

A

there are many different stem cells in different niches within the lungs
e.g. proximal and distal airways and alveoli

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17
Q

what is going wrong in cystic fibrosis?

A

anion channel mutations results in channels degradation in the ER - this channel would be fine if it could get to the surface

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18
Q

give two ways that people are trying to correct for disease causing mutations in CF

A
  1. using chaperone proteins to get receptor to surface

2. inhale active liposome to genetically modify epithelial cells using CRISPR to correct for the misfiling mutations

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19
Q

how are lung progenitors made from ES cells?

A

you need to copy development to generate particular types of cells
>once factors are added to narrow down the potency, lineage decision of lung of thyroid tissue is made

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20
Q

when you make lung cells from ES in a dish what will you see and what issues does this pose for medicine?

A

there will be a mixture of lung and thyroid tissue - its hard to direct them just to lung cells right now (could gain info from animal models)
>it is hard to see how you could control this in vivo

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21
Q

how could iPSC been used to rescue CF patients lungs?

A

> take skin fibroblasts
make iPSC
differentiation into ling epithelium
correct CFTR gene mutation
locally irradiate damaged patients cells
put these back into patient with scaffold

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22
Q

what chaperone proteins have been shown to rescue CFTR?

A

C18 - helps epithelium get channel to the surface and stops them being degraded
>rescues function of epithelium

23
Q

what can lung organoids be used for?

A

model development
model disease
test drugs

24
Q

what cell types home to sites of injury?

A

MSC - reduce inflammation, reduce scarring and increase tissue repair

25
Q

how do MSC modulate fibrosis?

A

they decrease the collagen accumulation

26
Q

how do MSC reduce inflammation?

A

supress pro-inflammatory and increase anti-inflammatory cytokines

27
Q

what two other functions do MSC have?

A

induce angiogenesis

recruit and activate T cells

28
Q

lungs are inflating and deflating all the time, how may this affect cells?

A
  • cytoskeleton remodelling
  • adhesions/loss-of adhesions
  • generation of force/relaxation
  • cell movement
    >this may result in change of gene expression - regulates proliferation and differentiation
29
Q

how is the effects of lungs inflating and deflating all the time implicated in disease?

A

some diseases affect how you breathe in and out and this will have a knock on affect on stem cell niches

30
Q

what signals into cells and so any force made on it will be signalled into cells? and what does this affect?

A

ECM - this will feed to nucleus

survival, proliferation, differentiation, adhesion and migration

31
Q

what implication on repopulating tissue will ECM have?

A

regulating this will be important

32
Q

human bronchial epithelial cells were kept in culture, what affect did cyclic stretch and compression have on them?

A

stop their spreading and migration but stimulate division

33
Q

human pulmonary endothelial cell line plated in 2D culture onto BioFlex, what two things were done and what affect did this have?

A
  1. cyclic stretch experiments
  2. blood flow shear stress stimulation
    saw changes in gene expression
34
Q

what is lunch on a chip?

A

a device lined with human cells that mimics the mechanical and chemical functions of a living, breathing lung

35
Q

describe the set up of lung on a chip?

A

> contains hollow channels
porous flexible membrane separates 2 channels
either side lined in human lung and capillary blood vessels cells
air flows over lung cells
liquid medium containing human white blood cells flows below the capillary cells layer

36
Q

how is breathing simulated in lung on a chip?

A

cyclic suction in side channels make sheet stretch and relax rhythmically

37
Q

when bacteria was introduced into the air channel of lung on a chip, what was seen?

A

WBS migrate into airways and engulf bacteria

38
Q

lung on a chip was used to model pulmonary oedema, what happens in this?
and how was this induced?

A

> fluid from the blood stream leaks into the air sacs

>cancer therapeutic IL2 is known to cause pulmonary oedema and so this was added to blood

39
Q

when lung on a chip was used to mimic airborn nanoparticles what did it predict?

A

breathing increases their absorption into the blood - this has also been shown in animal studies

40
Q

what does the ECM regulate?

A

migration and spreading, localised mechanical force and tissue properties

41
Q

what also cells to move over each other during regernation?

A

old ECM broken up and new one made rapidly by MMP

42
Q

what does disease and ageing affect and what affect does this have on repair?

A

disease/ageing may affect the ECM and so influence repair

43
Q

what can be used as a natural scaffold?

A

ECM - people are trying to mimic and improve this

44
Q

people want to find out more about how the ECM works, what is particular?

A

how it regulates tissue and stem cell niches

45
Q

how was rat lung ECM used as scaffold for new lung?

A

> strip ECM of cells using buffer solution
coat with epithelium and endothelium from rat host
when inserted back into rats these worked in vivo – maintain lung function

46
Q

what is the ECM mostly made of ?

A

collagen

47
Q

ECM has been used to make tracheas for humans, how was this done? and what was bad about this?

A

> ECM put in bioreactor to coat with patients cells
used to replace diseased trachea
Italian surgeon did this a few times
he did not carry out risk assessment or seek ethical approval
most people who received his treatment died

48
Q

people that donate tracheas may be old, why is this a problem when we want to use their ECM? and how will we overcome this in the future?

A

the scaffold changes with age

>3D printing scaffolds

49
Q

what was seen when neonatal rat lung epithelial cells were put on ECM scaffold? what happens when these were transplanted into rats?

A

they stuck to the scaffold, rapidly proliferated and rarely died
>no leaks, no trouble with circulation, gas exchange occurs for short period of time before they had to kill rat

50
Q

why did they need to kill rat so soon after operation?

A

under the ethical approval they had to be killed shortly after the operation
>rat was open and so susceptible to infection - this was to see how lungs would function

51
Q

what has been tried with lungs in terms of ECM?

A

humans lung segments from tissue banks
decellularised with buffer
seeded with lung cell lines
this looked pretty promising as cells adhered well
>this is being done on non-human promates

52
Q

what other organs has ECM been used in?

A

> the liver - shown to have similar function to liver, transplanted into rat, cells survived and function with minimal ischemic damage

53
Q

what approach is being made with heart valves?

A

> biodegradable scaffold
human cells
put into non human primates

54
Q

why are the heart values has to mimic and replace?

A

they are under a lot of pressure

SCRA (19 decks)

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