Tissue Regeneration & Repair Flashcards
What are labile cells?
- continuously capable of proliferating
- epithelial & stem cells (immortal)
What are stable cells?
- typically in G0
- can proliferate with a response to injury
What are permanent cells?
NO replication
What are the 2 important properties of stem cells?
self renewal & asymmetric replication
What is self renewal?
allows maintenance of functional population of precursors for long periods of time
Whcih stem cell porperty is telomerase positive?
self renewal
What are omnipotent (totipotent) stem cells?
1st few cells fertilized in embryo
What are pluripotent stem cells?
gives rise to cell derivatives of 3 germ layers; can do any tissue type
What are multipotent stem cells?
lineage specific
What are induced pluripotential cells?
reprogrammed to embyronic stem cell
What are th ekey regulators of the cell cycle?
cyclins
What gene is able to stop the cell cycle to allow repairs and is a repsonse to damage is activated?
P53
What are the characteristics of growth factors?
- short-lived
- pleiotropic (multiple physiologic behaviors)
- activate via autocrine, paracrine, and endocrine
What is the difference between autocrin, paracrine, and endocrine?
- autocrine: acts on itself
- paracrine: one cell acting on a neighbor
- endocrine: secreted form one tissue and travels a distance to the site
What is the epidermal growth factor (EGF)?
- stimulates collagen synthesis
- mitogenic for fibroblasts and endothelial cells
What is the platelet derived growth factor (PDGF)?
- competent factor (moves cells from G0 to G1)
- chemotactic
- induces moderate proliferation
- has proinflammatory properties
What is the fibroblast growth factor (FGF)?
- role in stimulating collagen synthesis
- role in fibroblast & monocyte proliferation
What is the transforming growth factor (TGF-alpha)?
binds to EGF receptor
What is the vascular endothelial growth factor (VEGF)?
- induces angiogenesis by rpomoting endotheliual cell proliferation
What is the role TGF-beta?
- can inhibit epithelial growth (promotes apoptosis)
- increases synthesis of collagen and fibronectin
What is the effect of a low conc. of TGF-beta?
induces synthesis and secretion of PDGF
What is the effect of a high conc. of TGF-beta?
decreases the expression of PDGF receptors
What are the characteristics of cytokines (IL-1 & TNF)?
- secreted by cells of immune system
- induce fibroblast proliferation
- chemotactic
- synthesize collagen
- TNF is angiogenic
The extracellular matrix is formed by proteins that do what?
- mechanical support
- sequester water and minerals
- regulate proliferation
The extracellular matrix is formed by proteins that do what?
- mechanical support
- sequester water and minerals
- regulate proliferation
What does the extracellular matrix consist of?
structural proteins & adhesive glycoproteins
What are the fibrous proteins in the extracellular matrix?
collagens & elastins
What are the proteoglycans and glycosaminoglycans in the extracellular matrix?
- proteo: dermatan sulfate & heparan sulfate
- glyco: hyaluronan & syndecan
What are the adhesive glycoproteins and receptors that connect matrix elements to one another?
- laminin (type 4 collagen in BM)
- fibronectin
- integrins
What are the types of fibrillar collagens?
types 1, 2, 3, 5
What are the types of non-fibrillar collagens?
type 4 found in basement mebranes
What deals with 3 post-translational ER?
pro-peptide to pro-collagen
What are the steps of collagen synthesis?
- signal peptide on N-terminal
- prolyl and lysyl hydroxylase produce hydroxyproline and hydroxylysine (requires vitamin C)
- propeptides twist into procollagen triple helix
What is the golgi apparatus modification?
last post-translational modification
What is the formation of tropcollagen?
membrane bound peptidases remove “loose ends” of procollagen
How is collagen fibril formed?
extracellular copper-dependent lysyloxidase acts on lysines & hydroxylysines that bond between tropcollagen
What types of collagen are known as interstitial collagenases?
types 1, 2, 3
What type of collagen is known as a gelatinase?
type 4
What are glycosaminoglycans bound to the cellular membrane by?
CD44
What are the 3 types of healing & repair?
- resolution
- regeneration
- repair by connective tissue
What is resolution?
- injury causing no tissue destruction (BM still intact)
- ex: mosquito bite
What is regeneration?
- tissue destruction without significant disruption of BM
- ex: mild sunburn
What is repair by connective tissue initiated by?
macrophages & TGF-beta
What is the sequence of repair by connective tissue?
- angiogenesis
- migration/proliferation of fibroblasts
- deposition/remodeling of EM
- remodeling of scar
During angiotensin, what is released?
MMPs & VEGF (secretes nitric oxide)
What is the function of Ang1 & Ang2?
stabilize vessels/recruitment of pericytes and smooth muscle cells
What are fibroblasts in connective tissue repair triggered by?
- PDGF
- EGF
- FGF
- TGF-beta
- cytokines
What is granulation tissue?
- 1st step in repairing “divot”
- connective tissue of neovascularization
What is covered by a scab and is evidence of re-epithelization?
granulation tissue
What are the functions of FGF?
- stimulates proliferation of endo cells, fibro, ECM deposition
- promoyes migration of macrophages and fibro to damaged area
- stimulates epithelial cell migration to cover wounds
What is the role of TGF in scar formation?
- stimulates production of collagen, fibronectin
- inhibits collagen degradation by decreasing MMPs
- anti-inflammatory
What is the role of MMPs in scar formation?
cleave ECM components
What is scar formation?
original tissue replaced by fibrous connective tissue
When does scar blanching occur?
regression of blood vessels
What can result in wound contraction?
differentiation of fibroblasts into myofibroblasts
What are the factors that affect tissue repair?
- infection
- glucocorticoids
- complications of tissue repair
- location/type of injury
- co-morbidities (diabetes, arthritis)
What are the complications of tissue repair?
- fibrosis
- keloid
- contracture
- pyogenic granuloma
What is fibrosis?
wound healing where dense CT replaces normal parenchymal tissue
Where is fibrotic scarring common?
after myocardial infarction
What is a keloid?
- exuberant collagen deposition related to defiency of matrix metalloproteinases
- rises up from scar tissue
What is a contracture?
excessive collagen deposition and myofibrolastic contraction
When does a contracture often occur?
in burn injuries
How does a pyogenic granuloma form?
arises from persistent granulation tissue
What is osteochondritis dissecans? (case study)
inflammation of bone and cartilage
What is drilling vs internal fixation vs salvage? (case study)
- drilling: into bone to disrupt margin and release growth factors
- internal fixation: uses metal or bioabsorbable devices to stabilize joint
- salvage: when cartilage is excessively deteriorated (OATS)
What drives differentiation of cord stem cells into chondrocytes/osteocytes? (case study)
bone morphogenic protein
What can be a significant complication of reconstructive surgery? (case study)
venous congestion
What does the patient with the ear bit off present?(case study)
post. auricular artery & super. temporal artery
