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BIEN 138: Wound Repair > Lecture 1-4 Notes > Flashcards

Lecture 1-4 Notes Flashcards

1
Q

When are office hours and informal office hours?

A

MWF 1-3; F 3-4pm

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2
Q

Wound repair is the body’s natural response to injury that, in tightly-orchestrated steps, aims to do what three things?

A
  1. Minimize tissue damage
  2. Drive wound closure
  3. Promote new tissue formation
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3
Q

Of the various tissues and organs, what is the most prone to wounding?

A

The skin

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4
Q

Skin is the largest and arguably the simplest organ in the body. What 3 things does it do for us?

A
  1. Acts as a barrier to pathogens
  2. Promotes thermal regulation and sensation to external stimuli
  3. Controls water evaporation
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5
Q

What three layers is the skin composed of?

A
  1. Epidermis
  2. Dermis
  3. Hypodermis or Subcutaneous layer
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6
Q

What cells does the epidermis consists of?

A

Keratinocytes, melanocytes (pigment), and langerhan cells (immune)

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7
Q

What cells does the dermis consist of?

A

Fibroblasts, blood and lymphatic vessels, nerves, and skin appendages

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8
Q

What are some examples of skin appendages?

A

Hair follicles, oil glands, and sweat glands

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9
Q

What cells does the hypodermis consist of?

A

Fibroblasts, adipocytes, and macrophages

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10
Q

What are the 4 steps to the wound repair cascade?

A
  1. Blood (fibrin) clot, inflammation, and re-epithelialization
  2. New tissue formation (granulation)
  3. Wound contraction
  4. Wound remodeling
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11
Q

True or false? Slow or non-healing wounds lack optimal granulation tissue.

A

True

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12
Q

What are the 4 key features that interfere with new tissue formation?

A
  1. Underlying pathology
  2. Chronic inflammation
  3. Lack of optimal neovascularization
  4. Bacterial colonization and biofilm formation
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13
Q

What do we mean when we say that underlying pathology can interfere with new tissue formation?

A

That any prior conditions, such as diseases or injuries, that a patient has may have can cause new tissue formation to not be carried out in the best way. An example of this is the glucotoxicity of immune or tissue cells in diabetes disrupting new tissue formation (granulation).

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14
Q

What are some tissue engineering strategies for enhancing wound repair?

A

Using viable cells to engineer new tissues and organs in vitro or in situ.

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15
Q

What is the different between adult wound repair and fetal wound regeneration?

A

Adult wounds will heal with a scar, while early-stage fetal wounds can undergo scarless regeneration

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16
Q

Define confluent monolayer and describe an experiment for wound repair.

A

A confluent monolayer means that you have cells forming a single layer on the bottom of a petri dish that don’t pile on top of each other. This type of cell culture experiment is used to demonstrate wound repair by scratching the surface and washing to monitor the process of closure of the wound. Pictures are taken at timely intervals of the wounded area to better describe the process.

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17
Q

What is the time frame for stage 1 (blood clotting, inflammation, and re-epithelization) of the wound repair cascade?

A

From 0.1 days up until 3 days

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18
Q

What is the time frame for stage 2 (granulation) of the wound repair cascade?

A

About 3 days up until 12 days.

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19
Q

What is the time frame for stage 3 (wound contraction) of the wound repair cascade?

A

About 8 days until almost 30 days

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20
Q

What is the time frame for stage 4 (wound remodeling) of the wound repair cascade?

A

From about 10 days until almost 300 days

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21
Q

True or false? The stages of the wound repair cascade happen strictly in order from 1-4.

A

False, the stages of the wound repair cascade overlap.

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22
Q

What are the key determinants of wound repair?

A

Cells, mechanical forces, soluble factors, and extracellular matrix (ECM)

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23
Q

What are the two classifications of cell types in tissues?

A

Parenchymal Cells and Stromal Cells

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24
Q

Define Parenchymal cell.

A

The primary functional unit of a tissue

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25
Q

Define Stromal cell

A

The structural or supporting unit of a tissue

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26
Q

True or false? Every tissue/organ has unique stromal cells.

A

False. Every tissue/organ has unique parenchymal cells though!

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27
Q

What is an example of 2 parenchymal cells that can be found in the brain?

A
  1. Neurons

2. Glial Cells

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28
Q

What is the function of neurons?

A

To process and transmit information via electrochemical signals

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29
Q

What is the function of glial cells?

A

To form myelin and protect neurons as well as to balance ions.

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30
Q

What can happen if something goes wrong with the neurons?

A

Parkinson’s Disease

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31
Q

What can happen if something goes wrong with the glial cells?

A

Alzheimer’s Disease

32
Q

What is an example of a parenchymal cell that is found in the heart?

A

Cardiomyocytes

33
Q

What is the function of cardiomyocytes?

A

To provide periodic, synchronized contraction to facilitate blood flow

34
Q

What can happen if cardiomyocytes don’t function properly?

A

Myocardial Infarction

35
Q

What are 3 examples of parenchymal cells in the musculo-skeletal system?

A
  1. Skeletal Muscle Cell
  2. Osteoclast
  3. Osteoblast
36
Q

What is the function of skeletal muscle cells?

A

To contract the muscles

37
Q

What is the function of osteoclasts?

A

To degrade bone and release minerals such as Ca2+ and PO4-

38
Q

What is the function of osteoblasts?

A

To form bone

39
Q

What can happen if any of the parenchymal cells in the musculo-skeletal system don’t function properly?

A

Osteoporosis

40
Q

What is a parenchymal cell found in the skin?

A

Keratinocytes

41
Q

What is the function of keratinocytes?

A

To form barriers against environmental factors such as pathogens and UV radiation

42
Q

What are the disease implications of keratinocytes not functioning properly?

A

Actinic keratosis or invasive squamous cell carcinoma

43
Q

List 4 types of stromal cells.

A
  1. Fibroblasts
  2. Endothelial cells
  3. Pericytes
  4. Inflammatory cells (infiltrating cells)
44
Q

What is the function of fibroblasts?

A

Fibroblasts secrete ECM consisting of proteins and carbohydrates

45
Q

What is the function of endothelial cells?

A

Endothelial cells form blood vessels and maintain normal blood flow to ensure nutrient and O2 supply as well as mediating tissue inflammation

46
Q

What is the function of pericytes?

A

To provide structural support to endothelial cells

47
Q

What is the function of inflammatory cells?

A

To secrete soluble factors that aid in pathogen removal as well as new cell proliferation and migration

48
Q

What are 2 disease implications if fibroblasts do not function properly?

A
  1. Keloids

2. Fibrochondrogenesis

49
Q

List some of the disease implications if endothelial cells or pericytes do not function properly. Be sure to include disease implications for both increased and decreased activity.

A

Increased Activity: cancer or diabetic retinopathy

Decreased Activity: peripheral limb ischemia, myocardial infarction, non-healing wounds

50
Q

List some examples of autoimmune diseases that can occur if inflammatory cells do not function properly.

A

Type 1 Diabetes, Crohn’s Disease, and Rheumatoid Arthritis

51
Q

True or false? During wound repair, stromal cells actively collaborate to orchestrate new tissue formation.

A

True

52
Q

Define ligand.

A

A soluble or insoluble molecule (protein, peptide, hormone, carbohydrate) that binds to a cell receptor

53
Q

Define cytokine.

A

A soluble ligand that binds to a cell and mediates cell signaling

54
Q

Define chemokine.

A

A chemotactic cytokine; a cytokine that induces directed cell migration

55
Q

Define growth factor.

A

A cytokine that stimulates cell growth, proliferation, or differentiation

56
Q

List 6 growth factors.

A
  1. TNF-a
  2. VEGF
  3. FGF
  4. PDGF
  5. KGF
  6. TGF-B
57
Q

What is TNF-a and what does it do?

A

TNF-a is the tumor necrosis factor alpha growth factor that helps with immune cell migration and activation

58
Q

What is VEGF and what does it do?

A

VEGF is vascular endothelial growth factor and it helps with endothelial cell proliferation, migration and angiogenesis

59
Q

What is FGF and what does it do?

A

FGF is fibroblast growth factor and it helps with endothelial cell proliferation, migration and angiogenesis

60
Q

What is PDGF and what does it do?

A

PDGF is platelet-derived growth factor and it helps with fibroblast migration and proliferation as well as blood vessel maturation

61
Q

What is KGF and what does it do?

A

KGF is keratinocyte growth factor and it promotes keratinocyte migration and proliferation

62
Q

What is TGF-B and what does it do?

A

TGF-B is transforming growth factor beta and in help with synthesizing the extracellular matrix

63
Q

What are the three cellular methods for signaling?

A

Autocrine, juxtacrine, endocrine and paracrine signaling

64
Q

Describe autocrine signaling.

A

The same cell secretes and receives a cytokine signal.

65
Q

Describe paracrine signaling.

A

A cytokine signal is secreted from one cell to a nearby cell.

66
Q

Define endocrine signaling.

A

A signal is secreted from one cell into the bloodstream where it can be detected by a target cell that is far away.

67
Q

Define juxtacrine signaling.

A

Signaling that takes place in close contact (signaling by gap junctions).

68
Q

What 2 things does the cytoskeleton do?

A
  1. Provides critical mechanostructural support to cells

2. Confers cells its equilibrium shape/form

69
Q

What 3 things is the cytoskeleton made of?

A

Actin filaments, microtubules and intermediate filaments

70
Q

How does the cytoskeleton dictate cell shape?

A

By establishing a cell-ECM force balance (the tensegrity model)

71
Q

Describe the cell-ECM force balance.

A

The tension in actin microfilaments (contractility) is equal to the sum of microtubule compression and cell-ECM adhesion strength (adhesiveness or stiffness). This describes the cell shape in equilibrium.

72
Q

How do we know that cells work as a tensegrity structure?

A

In fluorescently-labeled actin microfilaments we can see the residual tension through microscopy. We can also see Microtubule compression through similar methods.

73
Q

What are integrins?

A

Integrins are transmembrane receptors that facilitate cell-extracellular matrix (ECM) adhesion. Upon ligand binding, integrins activate signal transduction pathways that mediate cellular signals such as regulation of the cell cycle, organization of the intracellular cytoskeleton, and movement of new receptors to the cell membrane.[3] The presence of integrins allows rapid and flexible responses to events at the cell surface (e.g. signal platelets to initiate an interaction with coagulation factors).

74
Q

How do we know that cells act as a tensegrity structure through cutting actin microfilaments?

A

The filaments shrink back once they’re cut to maintain tension

75
Q

How do we know that cells act as a tensegrity structure through punching a hole in actin microfilaments?

A

The hole stretches with the actin microfilaments to maintain tension

76
Q

True or false? Higher cytoskeletal tension is exhibited on softer ECM.

A

False. Higher cytoskeletal tension is exhibited on stiffer ECM

BIEN 138: Wound Repair (2 decks)

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