tissue repair and wound healing

Question 1

difference b/w regeneration and healing

Answer 1

regeneration - restores normal tissue

healing can involve scar formation and fibrosis

Question 2

what is the role of extracellular matrix in regeneration and repair

Answer 2

must be intact for regeneration of normal tissue

if the matrix is damaged the injury is repaired by fibrous tissue deposition and scar formation = nodular regeneration

Question 3

what is resolution

Answer 3

when completed very little residual evidence of injury is noted

requires:
minimal tissue damage
neutralization of chemical mediators

Question 4

what does the inner cell mass form

Answer 4

the embryo (pluripotent stem cells)

Question 5

what are the totipotent cells

Answer 5

these are the earliest of stem cells (zygote)

these can make every tissue in the body and the placenta (fetal membranes)

Question 6

multipotent

Answer 6

more restricted than pluripotent
produce differentiated cells from the 3 embryonic layers

in cells of bone marrow in fetus and adult

Question 7

induced pluripotent stem cells (iPS) cells

Answer 7

differentiated cells that are reprogrammed into pluripotent cells

Question 8

adult stem cells

Answer 8

Present in tissues that continuously divide such as the bone marrow, skin and lining of the GI tract
Possibly present in liver, pancreas, adipose tissue
Generate rapidly dividing cells known as transit amplifying cells→ these cells lose the capacity of self-perpetuation and give rise to cells with restricted developmental potential known as progenitor cells

Question 9

what is transdifferentiation

Answer 9

A change in the differentiation of a cell from one type to another (metaplasia)

a) non-stem cell transforms into a different type of cell
b) already differentiated stem cell creates cells outside its already established differentiation path

Question 10

what is cell transduction

Answer 10

• Genes from a host cell (a bacterium) are incorporated into the genome of a bacterial virus (bacteriophage) and then carried to another host

Question 11

bone marrow stem cell types ? 2

Answer 11

Contains HSC’s (Hemopoietic Stem cells) and stromal cells (multipotent)
HSC’s: all blood cell lineages
Stromal cells: can generate chondrocytes, osteoblasts, adipocytes, myoblasts and endothelial cell precursors depending on the tissue to which they migrate

Question 12

liver stem cells?

what do these give rise to?

Answer 12

Stem cells/progenitor cells→ in the canals of Hering (junction b/w the biliary duct system and parenchymal hepatocytes)
Give rise to oval cells→ bipotential progenitors which can differentiate into hepatocytes and biliary cells
Liver stem cells act as a secondary or reserve compartment activated only when hepatocyte proliferation is blocked

Question 13

brain stem cells?

Answer 13

Neurogenesis from neural stem cells (NSC’s) occurs in the brain of adult rodents and humans
Located in the subventricular zone (SVZ) and the dentate gyrus of the hippocampus

Question 14

skin stem cells?

Answer 14

Stem cells are located in three different areas of the epidermis:

Hair follicle bulge

Interfollicular areas of the surface epidermis

Sebaceous glands

Question 15

intestinal epithelium stem cells location

Answer 15

Crypts are monoclonal structures derived from single stem cells: the villus is a differentiated compartment that contains cells from multiple crypts

Question 16

skeletal and cardiac muscle stem cells

Answer 16

Skeletal muscle mycotyes do not divide even after injury

Growth and regeneration of skeletal muscle occur by replication of satellite*** cells located beneath the myocyte basal lamina

Question 17

cornea stem cells

Answer 17

Limbal stem cells maintain the outermost corneal epithelium

These cells are located at the junction b/w the epithelium of the cornea and the conjunctiva

Question 18

inducing agents for VEGF

Answer 18

hypoxia
TGFbeta
PDGF
TGF alpha

Question 19

VEGF R3

Answer 19

on lymphatics

Question 20

what does VEGF stimulate

Answer 20

the tip cell

increased sprouting 
increased EC proliferation
INcreased EC survival
Decreased vascular organization
increases vascular permeability

Question 21

DLL4/Notch functions

Answer 21

via notch and DLL4 the tip cell will tell the stalk cell to stop replicating

DLL4/notch:
-decreased sprouting
-decrease EC proliferation 
-increase vascular lumen size (pericytes, smooth muscle cells)
increase vascular organization
maturation

Question 22

what are the 3 steps in cutaneous wound healing

Answer 22

inflammation
proliferation
maturation

Question 23

what occurs during inflammation in cutaneous wound healing ?

at what time do neutrophils appear

Answer 23

platelet adhesion and aggregation
formation of a clot in the surface of a wound

release of VEGF- increased permeability and edema

within 24 hours neturophils appear

Question 24

proliferation phase of cutaneous wound healing

when does granulation tissue form?

Answer 24

formation of granulation tissue 24-72 hours

proliferation and migraiton of CT cells

• occurs when repair by parenchymal regeneration alone cannot be accomplished
• neutrophils replaced with macrphages 48-96 hours

-migration of fibroblasts – divide and secrete collagen (Type III later replaced by type I)

Re-epithelization of the wound
24-48 hours spurs of epithelial cells move from the wound edge along the cut margins of the dermis depositing basement membrane components

Question 25

what is granulation tissue and what are its functions

Answer 25

soft, pink, granular

highly vascularized
leaky- so often edematous

inflammatory cells

minimal mature colllagen

function:
anti-infection
-fill the wound
replace necrotic tissue
vessels provide nutrients and cells

Question 26

maturation of cutaneous wound healing

Answer 26

ECM deposition
tissue remodeling–> MMP’s degrade ECM components
Scar formation
Wound contraction (Myofibroblasts)

Question 27

what occurs in scar formation

Answer 27

leukocyte infiltrate, increased vascularity and edema disappear during the 2nd week

increased accumulation of collagen

scar= pale, avascular, spindle-shaped fibroblasts, dense collagen, fragments of elastic tissue , no adnexal structures (hair follicles, sebaceous glands)

Question 28

which cytokines are involved in increased collagen synthesis and stimulating fibroblasts

Answer 28

TNF
IL-1
IL-4
IL-13

Question 29

what is the macrophages function during wound healing

Answer 29

dedbridement –> collagenase, elastase

phagocytosis–> ROS, nitric Oxide

cell recruitment and activation
-PDGF
TGF-beta
EGF
IGF 
cytokines (TNF, IL-1, IL-6,)
fibronectin

matrix synthesis-->
-TGF
EGF
PDGF
Cytokines (TNF, IL-1, IFN-gamma) 
arginase
collagenease
prostaglandins
NO

angiogenesis:
FGF, VEGF
TNF
NO

Question 30

after 3 months what is the wound strength

Answer 30

70-80 percent

Question 31

glucocorticoids do what in wound healing

Answer 31

inhibit collagen synthesis (although they do act as anti-inflammatory)

Question 32

vitamin c deficiency does what in wound healing

Answer 32

inhibits collagen synthesis and retards healing

Question 33

wound dehiscence

Answer 33

rupture of the wound
such as an abdominal suture and a cough/vomiting/etc. causing increased pressure

evisceration – intestine protrudes out

Question 34

what is exuberant granulation

Answer 34

“proud flesh”

formation of excessive amounts of granulation tissue which protrudes above the level of the surrounding skin and blocks re-epitheliziation

Question 35

what is a hypertrophic scar

Answer 35

accumulation of excessive amounts of collagen

generally forms after thermal or traumatic injury

Question 36

what is a keloid

Answer 36

scar tissue grows beyond the boundaries of the original wound and does not regress
more common in african americans

know what this looks like on a slide

Question 37

what are desmoids

Answer 37

exuberatnt proliferation of fibroblasts and other CT

lies in the inferface b/w benign proliferation and malignant tumors

Question 38

function of PDGFbeta

Answer 38

activates fibroblasts, smooth muscle cells, and monocytes for their proliferation and migration

stimulates production of MMP’s, fibronectin

wound contraction

Question 39

fibroblast growth factor

Answer 39

mitogenic for most mesenchymal cells and induces endothelial cell to release proteolytic enzyme, scarring

chemotactic for fibroblasts

angiogenesis

Question 40

epidermal growth factor

Answer 40

mitogenic for epithelial cells, fibroblasts, glial cells and SMC

granulation tissue formation

Question 41

transforming growth factor alpha

Answer 41

shares homology with EGF

stimulates replication of hepatocytes and most epithelial cells

Question 42

transforming growth factor beta

Answer 42

monocyte chemotaxis

fibroblast migration and replication

collagen synthesis

collagenase secretion

deposition and remodeling of ECM

inhibits production of MMP’s and keratinocyte proliferation

Question 43

vascular endothelial growth factor

Answer 43

grwoth of new blood vessels

increase vascular permeability

mitogenic for endothelial cells

Question 44

cytokines IL-1 and TNF in healing

Answer 44

induce fibroblast proliferation and collagen syntehsis

TNF can also stimulate angiogenesis and cachexia