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BME 301 - Physiology > Midterm > Flashcards

Midterm Flashcards

1
Q

What is regenerative engineering

A

control cell regenerative processes by modifying the structure and function of molecules (proteins, genes) to facilitate recovery from cell death induced disorder

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2
Q

What are cell differentiation and proliferation

A

cell proliferation is the process of increasing the cell number while cell differentiation is the process of forming a variety of cell types that have specific functions

Proliferation —> mitosis, all cells have the same phenotype

Differentiation —> one cell gave rise to distinct cells with different phenotypes

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3
Q

When do cells generate and regenerate

A

cell generation occurs in embryos

cell regeneration occurs in adults and ONLY occurs in response to cell death.

if there’s no cell death and cells regenerate it is CANCER

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4
Q

What is atherosclerosis

A

a disease of the arteries characterized by the deposition of plaques of fatty material on their inner walls.

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5
Q

Life expectancy of different cells

A

skin – a week
intestinal cells – a month
cardiomyocytes – decades (usually die in heart attack)

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6
Q

What is ischemia and what percentage is the max to have a working heart

A

This means some part of your body isn’t getting enough blood, so it’s not getting enough oxygen, either. It can happen in your brain, legs, and just about everywhere in between.

25% for having a working heart

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7
Q

What is angiogenesis

A

production of new blood vessels

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8
Q

How much time does cell death and regeneration take?

A

cell death takes abt 24 hrs and regeneration takes 3-5 days

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9
Q

what is blastocyst?

A

The blastocyst is a structure formed in the early development of mammals. which contais 30-40 cells in the inner cell mass

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10
Q

Two ways of control cell regeneration an why are they used

A
  1. PROMOTE cell regeneration (when cell death is the cause of disorder, ex: Alzheimer’s)
  2. INHIBIT cell regeneration (when cell regeneration is the cause of disorder, ex: cancer, atherosclerosis)
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11
Q

what are the 3 layers of cells in a blood vessel

A
  1. intima (smooth muscle cells);
  2. medial cells (endothelial cells)
  3. Adeventitia (fibroblasts)
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12
Q

what is atherogenesis and when is there no atherogenesis

A

process of atherosclerotic plaque formation (leads to coronary artery heart disease)

There is no atherogenesis under constant shear stress

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13
Q

what can blood flow pattern changes can cause

A

atherosclerosis or atherogenesis

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14
Q

regular shear stress in blood vessels

A

10 - 20 dymes/cm^2

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15
Q

What are the two biological basis for regenerative engineering

A
  1. all cells can regenerate

2. cell regeneration is triggered by cell death or some sort of stimulation

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16
Q

rates of regeneration of different cell types

A

Cardiomyocytes <1%/year
Blood cells 100%/100 days
epithelial cells regenerate pretty fast
neurons have really really low regeneration rate bc they are well differentiated

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17
Q

What do cell death or stimulation trigger

A

activate Growth factors and cytokines

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18
Q

How to control cell regeneration

A

cell signlaing. signal transduction

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19
Q

what are signals

A

protein
lipis (phospholipids)
Ca (most popular)

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20
Q

General mold of cell signal

A
  1. starting signal like environmental stimulus like injury or shear stress decrease
  2. cells will respond to starting signal and it will cause growth factor gene to increase, protein to increase and protein release to increase. (soluble proteins)
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21
Q

What causes activation of intracellular cast cascade signal and then what happens

A

the binding of growth factors to the receptor

then the C molecule activates transcription factors which go to the nucleus for cyclins/ gene mitosis

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22
Q

why regenerative engineering

A
  1. Timing

2. Level

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23
Q

explain the TIMING of why reg eng.

A

a) molecular: healthy humans don’t have al ot of growth factors or cytokines lying around so when injury occurs the cell need to o GENE EXPRESSION of GF whic takes 12-24 hrs
b) cellular: then, it takes 1 day to do MITOSIS and most cells are dead by then

then, 5 days from injury to REGENERATION (natural defficiency)

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24
Q

How can reg. eng, improve timing

A

can be used to accelerate the process of cell regeneration by injecting growth factors

At cellular levels, we can introduce mature liver cells

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25
Q

explain the LEVEL of why reg. eng.

A

neurons and cardiomyocytes are really hard to regenerate

fibroblasts regenerate pretty easily

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26
Q

what is a receptor

A

is a protein that receives and transduces signals (transmembrane or extracellular)

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27
Q

What is fibrosis

A

overproduction of fibroblast which causes

collagen overproduction
formation of permanent scar tissue

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28
Q

How does the brain repair damage

A

glial cells production and extracellular matrix

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29
Q

where do glial cells form

A

sub ventricular zone

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30
Q

How much time does it take neurons to die if there is no blood

A

within 5 minutes

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31
Q

Recite the steps after injury occurs

A
  1. injury
  2. inflamation
  3. endothelial cells permeability increase
  4. leukocytes infiltration
  5. produce cytokines
  6. fibroblasts regeneration and extracellular matrix
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32
Q

How regenerative engineering (3 ways)

A
  1. molecular level
  2. cellular level
  3. tissue/organs
33
Q

Name the two forms of MOLECULAR level regenerative engineering

A
  1. promote cell regeneration

2. inhibit cell regeneration

34
Q

explain how to promote cell regeneration (molecular level reg eng)

A
  1. gene editing: promote the expression of a specific gene to make cells create protein like growth factors and cytokines
  2. gene transfer: physically introduce genes into cells e.g. growth factor gene. (need a carrier, a promoter and enhancers to drive gene expression)
35
Q

What is a carrier

A

a plasmid that has human DNA introduced and a prmoter. 2 -3 kps (kilo base pairsI

36
Q

How to insert DNA

A
  1. restriction enzyme cut plasmid
  2. insert human gene and virus promoter sequence into plasmid
  3. use glass pipe to insert into a tissue or organ
37
Q

Where does plasmid go?

A

to the NUCLEUS of the cell (only the nucleus has the right environment)

38
Q

Where can plasmids be introduced?

A

can be introduced in the cytoplasm and they travel to the nucleus because proteins can grab plasmids and transport them to the nucleus area

39
Q

Do cells usually take plasmids?

A

cells usually take as many plasmids as possible but once they realize its not theirs, cells activate self protection mechanisms and plasmids are rejected or destroyed.

out of 100 plasmids, 20 would stay on the cell

40
Q

How much time does protein administration take?

A

2-4 hours and after proteinases kill the proteins which means that if you wnat to introduce genes to make proteins, you have to insert plasmids every 2-4 hours

41
Q

What is the only compatible cell with blood and why

A

ENDOTHELIAL cells
because of HEPERAN SULPHATE (an anticoagulant)
everything else causes blood to coagulate

42
Q

explain INHIBIT cell regeneration (molecular level reg eng)

A
  1. gene editing to make cells less active
  2. shut down one of the enhancer regions
  3. RNA interference: use siRNA
43
Q

what is siRNA

A

is a double stranded RNA, 20-25 base pairs

44
Q

whar is RISC

A

is a RNA-induced similarity complex.

siRNA and RISC break down the cell RNA which prevents the production of proteins

45
Q

Two ways of Cellular level reg eng

A
  1. Stem cells

2. mature cells (somatic)

46
Q

what is a totipotent stem cell

A

reallt powerful stem cell that can give rise to a baby

47
Q

levels of stem cells

A
  1. totipotent (can give rise to a baby)
  2. pluripotent (found in blastocyst)
  3. multipotent (found in tissue)
48
Q

what is embryonic stemm cells and where is it found

A

found in a 7 day old embryo
human embryonic stem cells collection has been banned since 2000 tho, there are embryonic stem cells collected befored 2000 and frozen

49
Q

How to get embryonic stem cells

A
  1. collection of blastocyst
  2. Culture (to infcrease the number of embryonic stem cells because for therapy you need thousands of cells and one blastocyst only has 32 esc)
50
Q

what are induced pluripotent stem cells

A

a type of pluripotent stem cell that can be generated directly from a somaticc cell like fibroblasts

51
Q

how to transform a fibroblast into a pluripotent stem cell

A

insert transcription factor in a plasmid and introduce it to the fibroblast

stem mass production and it transforms into a e.s.c. like cell

Can be used to induce cell regeneration

52
Q

How to culture embryonic stem cells

A
  • proliferation
  • need water, all salts, all nutrients (amino acids and lipids)
  • CO2 at 5% level because it is the concentration of CO2 in our body
  • O 21%
  • Human serum
  • feeder cell layer
53
Q

what is human serum? and why is it needed to culture e.s.c.?

A

is a circulating carrier of exogenous and endogenous liquids in the blood

it is needed because it contains growth factors

54
Q

What is a feeder cell layer and why is it needed in e.s.c. cultures

A

a feeder cell layer is any cell that can support e.s.c. growth
best feeder cells: embryonic fibrobalsts (stem cells

without feeder cells, e.s.c. would change their phenotypes and become less powerful

feeder cells are known to produce growth factors, adhesion molecules and extracellular matrix.

55
Q

How have e.s.c. delivery clinical trials been and why

A

Clinical trials have been disapointing (not provided good results
BECAUSE it is hard for new cells to work together and at the same time of existing cells. Also, we don’t understand how e.s.c. differentiate and we need to understand nature to change it.

56
Q

Explain Tissue/organ level cell regeneration

A

NEED:

  • Endothelial cells (intima)
  • Smooth muscle cells (media)
  • fibroblasts (adventitia) `
57
Q

What is atheroma and how does it develop?

A

atheroma is plaque and smooth muscle cells produce extracellular matrix

58
Q

where can adhesion molecules be found

A

in the surface of leukocytes and endothelial cells

59
Q

what is hyperlipidemia

A

high concentration of lipids

60
Q

why would leukocytes not adhere to epithelial cells>

A

Because of the high density of adhesion molecules

61
Q

How much time does it take to completely block an artery

A

10 - 20 years

62
Q

what is atherosclerosis

A

atherosclerosis occurs when a substance called plaque is formed in the artery wall. Overtime, the buildup narrows the artery and blocks blood flow through it

63
Q

What is myocardial infraction and why is it caused

A

it is a heart attack and it is caused mostly by embolisms

64
Q

what is an embolism

A

a cardiac embolism is an obstruction that travels from the heart to lodge in a blood vessel.

65
Q

when do you get myocardial ischemia

A

qhen plaque block 95% of the artery and it prevent the heart to get enough oxygens

66
Q

How much myocardial death can humans tolerate?

A

25%

67
Q

What is a TTC test and why is it used

A

it is a tetrazolium test used to differentiate betweeen metabolically active and inactive tissues

used to know how much tissue/cells are dead

in healthy cells you will see RED, if you see white, the cells are dead

68
Q

what does collagenase do

A

kill collagen

69
Q

What is TUNEL and why is it used

A

TUNEL is terminal transferase mediated dUTP nich end cabeling

TUNEL can be used to dye and see dying cells

from this you can plot cell count vs fluorescence

70
Q

What is a used to label cells?

A

Antibodies

71
Q

Composition of plaque

A

brittle composition, crystalline structure

72
Q

embolism regarding plaque

A

loose plaque pieces break and block a downstream artery. Level of heart attack depends on the size of the dislodged plaque and the location in which it blocks blood flow

73
Q

Atheroma vs. Coagulation

A

atheroma: takes decades to couple years, loose atheroma cause embolism

Coagulation: Rupture in the intimal/ endothelial cell injury
fibrin gel forms due to the polymerization of fibriogen

74
Q

Mice heart coronary heart disease simulation

A

Surgical ligation of a coronary artery: suture to tie off blood coronary artery
myocardial ischemia: permanent blockade of 2nd bifurcation of coronary artery

75
Q

What is angioplasty

A

angioplasty is a procedure used to open blocked coronary arteries caused by coronary artery disease

Ballon stuck into the blood vessel via catheter to open up the lumen by physically breaking the embolus

76
Q

what is a stent

A

a stent is a metal or plastic tube inserted into the lumen of an anatomic vessel or duct to keep the passageway open

77
Q

What is repurfusion

A

Reperfusion injury, is the tissue damage caused when blood supply returns to tissue after a period of ischemia or lack of oxygen

superoxide formation, one of the most toxic molecules in our body. causes aging

78
Q

peak of cardiomyocytes death

A

1 day

BME 301 - Physiology (1 decks)

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