tissue repair and wound healing Flashcards
difference b/w regeneration and healing
regeneration - restores normal tissue
healing can involve scar formation and fibrosis
what is the role of extracellular matrix in regeneration and repair
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
what is resolution
when completed very little residual evidence of injury is noted
requires:
minimal tissue damage
neutralization of chemical mediators
what does the inner cell mass form
the embryo (pluripotent stem cells)
what are the totipotent cells
these are the earliest of stem cells (zygote)
these can make every tissue in the body and the placenta (fetal membranes)
multipotent
more restricted than pluripotent
produce differentiated cells from the 3 embryonic layers
in cells of bone marrow in fetus and adult
induced pluripotent stem cells (iPS) cells
differentiated cells that are reprogrammed into pluripotent cells
adult stem cells
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
what is transdifferentiation
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
what is cell transduction
• Genes from a host cell (a bacterium) are incorporated into the genome of a bacterial virus (bacteriophage) and then carried to another host
bone marrow stem cell types ? 2
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
liver stem cells?
what do these give rise to?
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
brain stem cells?
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
skin stem cells?
Stem cells are located in three different areas of the epidermis:
Hair follicle bulge
Interfollicular areas of the surface epidermis
Sebaceous glands
intestinal epithelium stem cells location
Crypts are monoclonal structures derived from single stem cells: the villus is a differentiated compartment that contains cells from multiple crypts
skeletal and cardiac muscle stem cells
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
cornea stem cells
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
inducing agents for VEGF
hypoxia
TGFbeta
PDGF
TGF alpha
VEGF R3
on lymphatics
what does VEGF stimulate
the tip cell
increased sprouting increased EC proliferation INcreased EC survival Decreased vascular organization increases vascular permeability
DLL4/Notch functions
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
what are the 3 steps in cutaneous wound healing
inflammation
proliferation
maturation
what occurs during inflammation in cutaneous wound healing ?
at what time do neutrophils appear
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
proliferation phase of cutaneous wound healing
when does granulation tissue form?
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
what is granulation tissue and what are its functions
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
maturation of cutaneous wound healing
ECM deposition
tissue remodeling–> MMP’s degrade ECM components
Scar formation
Wound contraction (Myofibroblasts)
what occurs in scar formation
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)
which cytokines are involved in increased collagen synthesis and stimulating fibroblasts
TNF
IL-1
IL-4
IL-13
what is the macrophages function during wound healing
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
after 3 months what is the wound strength
70-80 percent
glucocorticoids do what in wound healing
inhibit collagen synthesis (although they do act as anti-inflammatory)
vitamin c deficiency does what in wound healing
inhibits collagen synthesis and retards healing
wound dehiscence
rupture of the wound
such as an abdominal suture and a cough/vomiting/etc. causing increased pressure
evisceration – intestine protrudes out
what is exuberant granulation
“proud flesh”
formation of excessive amounts of granulation tissue which protrudes above the level of the surrounding skin and blocks re-epitheliziation
what is a hypertrophic scar
accumulation of excessive amounts of collagen
generally forms after thermal or traumatic injury
what is a keloid
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
what are desmoids
exuberatnt proliferation of fibroblasts and other CT
lies in the inferface b/w benign proliferation and malignant tumors
function of PDGFbeta
activates fibroblasts, smooth muscle cells, and monocytes for their proliferation and migration
stimulates production of MMP’s, fibronectin
wound contraction
fibroblast growth factor
mitogenic for most mesenchymal cells and induces endothelial cell to release proteolytic enzyme, scarring
chemotactic for fibroblasts
angiogenesis
epidermal growth factor
mitogenic for epithelial cells, fibroblasts, glial cells and SMC
granulation tissue formation
transforming growth factor alpha
shares homology with EGF
stimulates replication of hepatocytes and most epithelial cells
transforming growth factor beta
monocyte chemotaxis
fibroblast migration and replication
collagen synthesis
collagenase secretion
deposition and remodeling of ECM
inhibits production of MMP’s and keratinocyte proliferation
vascular endothelial growth factor
grwoth of new blood vessels
increase vascular permeability
mitogenic for endothelial cells
cytokines IL-1 and TNF in healing
induce fibroblast proliferation and collagen syntehsis
TNF can also stimulate angiogenesis and cachexia
