Repair

Question 1

What is repair?

Answer 1

restoring normal structure and function (healing)

Question 2

What are the two. often interconnected, process of repair?

Answer 2

Regeneration and Scar formation

Question 3

Define Regeneration

Answer 3

proliferation and differentiation of new cells from
stem cells to restore native tissue

Question 4

Define Scar formation

Answer 4

deposition of connective tissue (mostly collagen)

Question 5

Repair is tied to _____________ and must be tightly controlled

Answer 5

inflammatory response

Question 6

If repair is ________ or defective then _________ occurs

Answer 6

Insufficient, loss of structure/function

Question 7

If repair is ________ or defective then _________ occurs

Answer 7

excessive (fibrosis), loss of structure/function

Question 8

The central players in repair are:

Answer 8

Macrophages

Question 9

In terms of proliferative capacity, the tissue can be: (Three types)

Answer 9

• Continuously dividing tissues (labile tissues)
• Stable Tissues
• Permanent Tissues

Question 10

Define Continuously dividing tissues (labile tissues)

Answer 10

tissue that is constantly being lost and replaced by maturation from stem cells or mature cells

Question 11

Examples of Continuously dividing tissues (labile tissues)

Answer 11

skin, oral cavity, vagina, cervix,
exocrine ducts, GI tract

(Can often get regeneration in these types of tissues depending on the degree of injury)

Question 12

Define stable tissue

Answer 12

• Are normally not dividing (quiescent)
• Can regenerate to a limited degree in response to injury
  Exception: Liver (near
  complete regeneration via
  hyperplasia)

Question 13

Examples of stable tissue

Answer 13

endothelial cells, fibroblasts, smooth muscle, parenchyma (functional part) of most solid organs (kidney, pancreas, liver).

Question 14

Define permanent tissue

Answer 14

Do not proliferate after birth having become fully mature or terminally differentiated

Question 15

Examples of permanent tissue

Answer 15

neurons, cardiac muscle, skeletal muscle

Question 16

The size of cell populations are tightly regulated by ___________

Answer 16

the cell cycle

Question 17

Upon stimulation by _________ and regulation by ______, cells arrested in the G0 or G1
phase divide then differentiate

Answer 17

growth factors, cyclins

Question 18

What are the five phases of the cell cycle?

Answer 18

G0, G1, S, G2, and M

Question 19

In simple terms, G0 is:

Answer 19

quiescent phase (no division)

Question 20

In simple terms, G1 is:

Answer 20

presynthetic growth phase

Question 21

In simple terms, S is:

Answer 21

DNA synthesis phase

Question 22

In simple terms, G2 is:

Answer 22

premitotic growth phase

Question 23

In simple terms, M is:

Answer 23

mitotic phase

Question 24

Three effects of cyclins on the cell cycle:

Answer 24

• Cyclins are constantly being rapidly produced and degraded
• Cyclins activate cyclindependent kinases (CDKs) which phosphorylate regulatory proteins leading to cell division
• Cyclin-dependent kinase (CDK) inhibitors stop the cell cycle

Question 25

If damage is excessive or if tissues can’t repair by regeneration then they repair by _______________

Answer 25

scar formation

Question 26

Scarring is the:

Answer 26

replacement of non-regenerated cells with connective tissue

Question 27

Define fibrosis

Answer 27

excessive collagen deposition due to chronic inflammation (kidney, lungs, liver) or after necrosis (e.g. myocardial infarction)

Question 28

What is "organization" in scar formation?

Answer 28

fibrosis in a tissue space with an inflammatory exudate. (e.g. organizing pneumonia)

Question 29

What are the components of scare tissue?

Answer 29

capillaries and immature fibroblasts

Question 30

After clot formation occurs immediately after injury, what is the repair sequence? (Day 1, 2, 3-6, 7, and 14)

Answer 30

Day 1- Neutrophils migrate in and phagocytose foreign substances and necrotic tissue Day 2- macrophages enter, granulation tissue (capillaries and immature fibroblasts) starts to form, protected by a fibrin clot Day 3-6- lymphocytes and plasma cells enter Day 7- clot digested, initial repair complete Day 14- fibroblasts mature, collagen remodeled forming scar tissue (dense/white)

Question 31

Blood vessel growth (angiogenesis) is mediated by _________

Answer 31

vascular endothelial growth factor (VEGF)

Question 32

migration and proliferation of fibroblasts are mediated by ___________

Answer 32

fibroblast growth factor (FGF)

Question 33

By day 3-5 post injury, new _______ and ________ are formed giving a red/pink and granular appearing tissue “________ tissue”

Answer 33

blood vessels (capillaries), fibroblasts, granulation (fibroblasts include specialized fibroblasts with contractile properties called myofibroblasts)

Question 34

Fibroblast maturation/differentiation is stimulated by _________

Answer 34

TGF-β

Question 35

Fibroblast maturation/differentiation causes ________ deposit leading to ____________

Answer 35

collagen, termination of the inflammatory response

Question 36

Maturation, reorganization/remodeling into a scar begins ________ after injury and may continue for _________

Answer 36

2-3 weeks, months to years

Question 37

What are the types of repair?

Answer 37

Primary Intention and secondary Intention

Question 38

Characteristics and example of Primary Intention

Answer 38

- Little loss of tissue occurs with injury. - Wound margins are joined closely together. (Example: surgical incision)

Question 39

Characteristics and example of Secondary Intention

Answer 39

- Tissue is lost preventing edges of injury from being brought back together. (Example: extraction site) - increased granulation tissue and scar tissue

Question 40

New vessels are ______ due to VEGF and_________. Thus, granulation tissue is edematous in its early stages

Answer 40

leaky, incomplete interendothelial junctions

Question 41

Inflammatory cells (e.g. macrophages) make _________ which causes _________ recruitment and activation to make ___________

Answer 41

growth factors, fibroblast, connective tissues

Question 42

Over time, new vessels and proliferating fibroblasts __________ (increase/decrease), while ________ production increases eventually leading to a __________

Answer 42

decrease, collagen, pale avascular scar

Question 43

Four important growth factors in scar formation:

Answer 43

TGF-β, PDGF, FGF, and Cytokines

Question 44

(T/F) TGF-β has different effects depending on cell and tissue state.

Answer 44

True

Question 45

In both acute and chronic inflammation, TGF-β ________ production of and ________ breakdown of ECM

Answer 45

stimulates, inhibits

Question 46

TGF-β also had __________ effects where it _______ inflammatory responses

Answer 46

anti-inflammatory, ends

Question 47

PDGF stimulates the migration and proliferation of _______ and ________

Answer 47

fibroblasts, smooth muscle cells

Question 48

FGF _________ (stimulates/inhibits) fibroblast migration

Answer 48

stimulates

Question 49

Cytokines- IL-13 stimulates ___________ and fibroblast migration

Answer 49

collagen synthesis

Question 50

(T/F) Connective tissues are modified over time, thus balancing production and degradation

Answer 50

True

Question 51

_______________ are an important player in remodeling

Answer 51

Matrix metalloproteinases (MMPs)

Question 52

Talk about Matrix metalloproteinases (MMPs).

Answer 52

- released as inactive precursors (zymogens) - activated by proteases at the site of injury (e.g. plasmin) - degrade ECM proteins - then quickly inhibited by tissue inhibitors of metalloproteinases (TIMPs)

Question 53

What are the eight factors that can prevent or inhibit normal healing/repair?

Answer 53

- Infection: most important clinical cause - Nutrition: protein or vitamin C deficiency - Steroid use: anti-inflammatory (may inhibit healing) - Poor perfusion: atherosclerosis, diabetes - Foreign bodies: impede healing - Type and extent of injury: permanent tissues scar - Location of injury: resolution of tissue space inflammation - Aberration of cell growth: keloids or excessive granulation tissue (pyogenic granuloma)

Question 54

What are stem cells?

Answer 54

Undifferentiated cells capable of self-renewal and differentiation into mature (specialized) cells

Question 55

What are the three types of stem cells?

Answer 55

Totipotent, Pluripotent, and Multipotent

Question 56

Totipotent stem cells can differentiate into:

Answer 56

embryonic and extra-embryonic tissues

Question 57

Pluripotent stem cells includes:

Answer 57

embryonic SC and induced pluripotent SC

Question 58

Multipotent stem cells includes:

Answer 58

mesenchymal stem cells

Question 59

Embryonic stem cells (ES cells) has ________ capacity to form cells of ___________

Answer 59

Pluripotent, 3 germ layers

Question 60

Embryonic stem cells (ES cells) are ____________ and typically cause an __________ when placed in a different person

Answer 60

harder to isolate (inner cell layer of the blastocyst), immune response

Question 61

Where are Mesenchymal Stem Cells found?

Answer 61

within an organ or tissue with renewal capacity

Question 62

Mesenchymal Stem Cells maintain tissue ___________

Answer 62

homeostasis

Question 63

Mesenchymal Stem Cells are Controlled by other cells within the tissue niche. Give two examples.

Answer 63

- Hematopoietic stem cells- can be isolated from blood or bone marrow; and used in bone marrow transplants to treat leukemia/lymphoma - Bone marrow also contains mesenchymal stem cells (MSC) which give rise to bone, cartilage, fat, and muscle.

Question 64

What are iPS cells?

Answer 64

Reprogramed adult cells to acquire “stem-cell-ness”→ induced pluripotent stem cells (iPS cells) which should engraft and replace damaged cells

Question 65

What are the current applications of iPS cells?

Answer 65

- Being used in clinical trials to treat many diseases including macular degeneration, heart disease, Parkinson disease, spinal cord injury - A lot in the future!

Question 66

Dental application of iPS cells?

Answer 66

Mesechymal stem cells

Question 67

Clinical trials of Mesechymal stem cells have been very promising. Three of the dental applications are:

Answer 67

- engineer bone for orofacial bone regeneration. - tooth root regeneration - regeneration of pulp tissue in cleaned root canals with fabricated vital dental pulp tissue constructs (future “regenerative” endo treatment) Fun fact: Multiple companies allow you to bank teeth for future applications (~$300 + $13/month)

Question 68

Other applications of Mesechymal stem cells:

Answer 68

CNS disorders, repair infarcted myocardium, liver disease, autoimmune diseases…so many possibilities