Repair Flashcards
What is repair?
restoring normal structure and function (healing)
What are the two. often interconnected, process of repair?
Regeneration and Scar formation
Define Regeneration
proliferation and differentiation of new cells from
stem cells to restore native tissue
Define Scar formation
deposition of connective tissue (mostly collagen)
Repair is tied to _____________ and must be tightly controlled
inflammatory response
If repair is ________ or defective then _________ occurs
Insufficient, loss of structure/function
If repair is ________ or defective then _________ occurs
excessive (fibrosis), loss of structure/function
The central players in repair are:
Macrophages
In terms of proliferative capacity, the tissue can be: (Three types)
- Continuously dividing tissues (labile tissues)
- Stable Tissues
- Permanent Tissues
Define Continuously dividing tissues (labile tissues)
tissue that is constantly being lost and replaced by maturation from stem cells or mature cells
Examples of Continuously dividing tissues (labile tissues)
skin, oral cavity, vagina, cervix,
exocrine ducts, GI tract
(Can often get regeneration in these types of tissues depending on the degree of injury)
Define stable tissue
- Are normally not dividing (quiescent)
- Can regenerate to a limited degree in response to injury
Exception: Liver (near
complete regeneration via
hyperplasia)
Examples of stable tissue
endothelial cells, fibroblasts, smooth muscle, parenchyma (functional part) of most solid organs (kidney, pancreas, liver).
Define permanent tissue
Do not proliferate after birth having become fully mature or terminally differentiated
Examples of permanent tissue
neurons, cardiac muscle, skeletal muscle
The size of cell populations are tightly regulated by ___________
the cell cycle
Upon stimulation by _________ and regulation by ______, cells arrested in the G0 or G1
phase divide then differentiate
growth factors, cyclins
What are the five phases of the cell cycle?
G0, G1, S, G2, and M
In simple terms, G0 is:
quiescent phase (no division)
In simple terms, G1 is:
presynthetic growth phase
In simple terms, S is:
DNA synthesis phase
In simple terms, G2 is:
premitotic growth phase
In simple terms, M is:
mitotic phase
Three effects of cyclins on the cell cycle:
- 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
If damage is excessive or if tissues can’t repair by regeneration then they repair by _______________
scar formation
Scarring is the:
replacement of non-regenerated cells with connective tissue
Define fibrosis
excessive collagen deposition
due to chronic inflammation (kidney, lungs, liver) or after necrosis (e.g. myocardial infarction)
What is “organization” in scar formation?
fibrosis in a tissue space with an
inflammatory exudate. (e.g. organizing pneumonia)
What are the components of scare tissue?
capillaries and immature fibroblasts
After clot formation occurs immediately after injury, what is the repair sequence? (Day 1, 2, 3-6, 7, and 14)
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)
Blood vessel growth (angiogenesis) is mediated by _________
vascular endothelial growth factor (VEGF)
migration and proliferation of fibroblasts are mediated by ___________
fibroblast growth factor (FGF)
By day 3-5 post injury, new _______ and ________ are formed giving a red/pink and granular appearing tissue “________ tissue”
blood vessels (capillaries), fibroblasts, granulation
(fibroblasts include specialized fibroblasts with contractile properties called myofibroblasts)
Fibroblast maturation/differentiation is stimulated by _________
TGF-β
Fibroblast maturation/differentiation causes ________ deposit leading to ____________
collagen, termination of the
inflammatory response
Maturation, reorganization/remodeling into a scar begins ________ after injury and may continue for _________
2-3 weeks, months to years
What are the types of repair?
Primary Intention and secondary Intention
Characteristics and example of Primary Intention
- Little loss of tissue occurs with injury.
- Wound margins are joined closely together.
(Example: surgical incision)
Characteristics and example of Secondary Intention
- Tissue is lost preventing edges of injury from being brought back together. (Example:
extraction site) - increased granulation tissue and scar tissue
New vessels are ______ due to VEGF and_________. Thus, granulation tissue is
edematous in its early stages
leaky, incomplete
interendothelial junctions
Inflammatory cells (e.g. macrophages) make
_________ which causes _________ recruitment and activation to make ___________
growth factors, fibroblast, connective tissues
Over time, new vessels and proliferating fibroblasts __________ (increase/decrease), while ________ production
increases eventually leading to a __________
decrease, collagen, pale avascular
scar
Four important growth factors in scar formation:
TGF-β, PDGF, FGF, and Cytokines
(T/F) TGF-β has different effects depending on cell and tissue
state.
True
In both acute and chronic inflammation, TGF-β ________
production of and ________ breakdown of ECM
stimulates, inhibits
TGF-β also had __________ effects where it _______ inflammatory responses
anti-inflammatory, ends
PDGF stimulates the migration and proliferation of _______ and ________
fibroblasts, smooth muscle cells
FGF _________ (stimulates/inhibits) fibroblast migration
stimulates
Cytokines- IL-13 stimulates ___________ and fibroblast migration
collagen synthesis
(T/F) Connective tissues are modified over time, thus
balancing production and degradation
True
_______________ are an important player in remodeling
Matrix metalloproteinases (MMPs)
Talk about Matrix metalloproteinases (MMPs).
- 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)
What are the eight factors that can prevent or inhibit
normal healing/repair?
- 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)
What are stem cells?
Undifferentiated cells capable of self-renewal and differentiation into mature (specialized) cells
What are the three types of stem cells?
Totipotent, Pluripotent, and Multipotent
Totipotent stem cells can differentiate into:
embryonic and extra-embryonic tissues
Pluripotent stem cells includes:
embryonic SC and induced pluripotent SC
Multipotent stem cells includes:
mesenchymal stem cells
Embryonic stem cells (ES cells) has ________ capacity to form cells of ___________
Pluripotent, 3 germ layers
Embryonic stem cells (ES cells) are ____________ and typically cause an __________ when placed in a different person
harder to isolate (inner cell layer of the blastocyst), immune response
Where are Mesenchymal Stem Cells found?
within an organ or tissue with renewal capacity
Mesenchymal Stem Cells maintain tissue ___________
homeostasis
Mesenchymal Stem Cells are Controlled by other cells within the tissue niche. Give two examples.
- 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.
What are iPS cells?
Reprogramed adult cells to acquire
“stem-cell-ness”→ induced pluripotent stem cells (iPS cells) which should engraft and replace damaged cells
What are the current applications of iPS cells?
- Being used in clinical trials to treat many diseases including macular degeneration, heart disease, Parkinson disease, spinal cord injury
- A lot in the future!
Dental application of iPS cells?
Mesechymal stem cells
Clinical trials of Mesechymal stem cells have been very promising. Three of the dental applications are:
- 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)
Other applications of Mesechymal stem cells:
CNS disorders, repair infarcted myocardium, liver disease, autoimmune diseases…so many possibilities
