Regeneration and Repair Flashcards
How can regeneration be defined?
As the proliferation of dead or damaged cells by functional, differentiated cells or tissues in which normal structure is restored.
What are differentiated cells derived from?
Stem cells
What is repair a response to?
An injury involving both regeneration and scar formation (fibrosis)
What does repair lead to?
Permanent alternation in normal structure
How much can stem cells proliferate?
Potentially limitless
What happens to daughter stem cells?
They either remain as a stem cell, or differentiate into a specialised cell type
What is the importance of some daughter stem cells remaining as stem cells?
To maintain the stem cell pool
What happens to stem cells in early life?
They develop into many different cell types
What can stem cells be said to be?
An ‘internal repair system’
What is the purpose of the internal repair system produced by stem cells?
To replace or damaged cell tissues
What is the potential therapeutic utility of stem cells?
In degenerative disease
What does unipotent mean?
Only able to produce one type of differentiated cell
What does multipotent mean?
Able to produce several types of differentiated cells
What does totipotent mean?
Able to produce any cell type
What cells are totipotent?
Embryonic stem cells
Give two examples of where stem cells are found in a mature human?
Bases of crypts
Hematopoietic ontogeny
What happens to stem cells in the bases of crypts?
They produce new cells at the bottom, which then move up and undergo apoptosis, meaning the crypts are constantly regenerating
What happens in haematopoietic ontogeny?
Multipotent stem cells in the bone marrow can produce cells within their lineage
Clinically, what is haemtopoietic ontogeny good for?
Therapeutics
How can haemopoietic ontogeny be useful therapeutically?
It can be used to reconstitute bone marrow is it has been depleted.
Bone marrow can be removed from one patient and infused into another
Is the propensity to regenerate the same among all cell types?
No, it varies
What happens to labile cells?
They are continuously dividing
What is the purpose of the continual division of labile cells?
They are replacing cells that have been destroyed by apoptosis
Give two examples of cells that are labile
Epithelial
Haemopoietic
What is the normal state for labile cells
Cell division (G1-M-G2)
What do labile cells usually display?
Rapid proliferation
What state are stable cells usually in?
The resting state (G0) - they have not get entered the cell cycle
Can stable cells undergo division?
Yes, if appropriately stimulated
Give 3 example of stable cells
Hepatocytes
Osteoblasts
Fibroblasts
What is the speed of regeneration for stable cells?
Usually quite low, but depends on the stimuli exposed to
What state are permanent cells in?
G0
Are permanent cells capable of dividing?
No
Give 2 examples of permanent cells?
Neurones
Cardiac myocytes
When are permanent cells produced?
During embryonic development
Give an example of a response of a permanent cell?
Compensatory hyperplasia
What happens in compensatory hyperplasia?
Not producing new cells, but existing cells get bigger
Where does compensatory hyperplasia occur?
In the liver
What is each phase dependant on in the cell cycle?
Activation and completion of the previous stage
What is advantage of each stage of the cell cycle being dependant on completion of the previous stage?
Helps prevent reduplication of abnormalities such as mutations
Where are there checkpoints in the cell cycle?
Between G1 and S
Between G2 and M
What is the purpose of the checkpoint between G1 and S?
The integrity of DNA is monitored before it’s replicated
What is the purpose of the checkpoint between G2 and M?
DNA is checked after it’s replicated to ensure its safe to continue
What happens in alcoholic cirrhosis of the liver?
The ability of division is shown, as you get scarring that forms fibrous bands that surround nodules that contain numerous dividing hepatocytes. This gives the nodular nature of a cirrhotic liver.
What is the problem with studying the factors that control regeneration?
They are complex and poorly understood
Give two factors that control regeneration?
Growth factors
Contact between basement membrane and adjacent cells
What do growth factors do?
Help drive proliferation in the stem cell population
What do growth factors function as?
Ligands binding to specific receptors
What happens when a growth factor binds to its specific receptor?
They deliver extracellular signals to their target cells to stimulate the transduction of genes that control the cell cycle and progression
What is the process of growth factors controlling the cell cycle known as?
Receptor mediated signal transduction
Give two types of molecules that growth factors can be?
Proteins
Hormones
Give two examples of protein growth factors
EGF (epidermal growth factor)
PDGF (platelet derived growth factor)
What does EGF do?
Mitogenic for keratinocytes and fibroblasts, and so stimulates the formation of granulation tissue
What is EGF produced by?
Keratinocytes and macrophages, and other inflammatory cells attracted to the area of damage
What does PDGF do?
Causes the migration and proliferation of lots of cells that help with inflammation and healing of skin wounds
Where is PDGF stored?
Platelet granules
When does PDGF get released?
When platelets become activated
Give 3 examples of hormones that can act as growth factors
Oestrogen
Testosterone
Growth hormone
What kinds of hormones can growth factors be?
Autocrine
Paracrine
Endocrine
What does an autocrine hormone do?
Acts on the cell that produced it
What do paracrine hormones do?
Acts on the cells adjacent to the one that produced it that have the appropriate receptor
What do endocrine hormones do?
Travel in the blood and act on cells far away from the original site of production
How does contact between basement membranes and adjacent cells control regeneration?
There is signalling through adhesion molecules, which inhibits proliferation in intact tissue
What is the control of regeneration by contact between the basement membrane and adjacent cells known as?
Contact inhibition
Where are regenerative control mechanisms deranged?
Cancer
What is fibrous repair?
The replacement of functional tissue by scar tissue
When do fibrous repair and scarring occur?
When there is necrosis of permanent cells, or when there is a necrosis of labile or stable cells which leads to the collagen framework being destroyed
Why does a destruction in collagen framework lead to scarring?
Because you get deposition of collagen to replace the framework
What are the key components of fibrous repair?
Cell migration and inflammation
Angiogenesis
Extracellular matrix production and remodelling
Why is cell migration important in fibrous repair?
Need to get cells there so they can exert their effects
What are the cell types in fibrous repair?
Inflammatory cells
Endothelial cells
Fibroblasts and myofibroblasts
What inflammatory cells are involved in fibrous repair?
Neutrophils
Macrophages
Lymphocytes
What is the purpose of neutrophils and macrophages in fibrous repair?
Phagocytosis of debris
What is the purpose of lymphocytes and macrophages in fibrous repair?
Chemical mediators
What do chemical mediators do?
Attract other cells
What is the purpose of the endothelial cells in fibrous repair?
Angiogenesis
What is the purpose of (myo)fibroblasts in fibrous repair?
Extracellular matrix production
Wound contraction
What is angiogenesis known as in utero?
Vasculogenesis
Why is the development of a blood supply vital for wound healing?
It provides access for inflammatory cells and fibroblasts
Allows delivery of oxygen and nutrients
What is angiogenesis initiated by?
Proangiogenic growth factors
Give an example of a proangiogenic growth factor
VEGF
What happens to pre-exisiting vessels in angiogenesis?
They sprout new vessels
What are the stages of angiogenesis
- Vasodilation of pre-exisiting vessels in response to nitric oxide
- Endothelial proteolysis of basement membrane
- Migration of endothelial cells via chemotaxis towards the angiogenic stimulus of VEGF
- Endothelial proliferation
- Endothelial maturation and tubular regeneration
- Recruitment of periendothelial cells
What is the importance of endothelial maturation and tubular regeneration?
So can form a tubular structure that blood can flow through
What do periendothelial cells do?
Make the outer layers of vessels
What do periendothelial cells consist of?
Pericytes and vascular smooth muscle cells