Tissue Injury and Repair 1 Flashcards
Basic mechanisms. -Definitions of repair, regeneration, healing with scar formation. -How to describe the cell cycle. -Definitions and some examples of labile, stable and permanent tissues and their cellular response to injury. -Nature and function of stem cells -At least one example of stem cell use in clinical veterinary medicine.
REPAIR
Restoration of tissue structure and function after an injury. There are two possible reactions:
- REGENERATION- replacement of normal components and return to a normal state.
- SCAR TISSUE FORMATION- fibrous tissue, seen if tissues are incapable of complete restitution, or if tissues are capable of regeneration but supporting structures are severely damaged.
Usually both reactions contribute to repair in varying degrees.
WHAT DOES REPAIR REQUIRE?
Cellular proliferation
Interactions between various cells
Interactions between cells and extracellular matrix (ECM)
CELLULAR PROLIFERATION
Several types of cells proliferate
Remnants of normal tissue will attempt to restore normal structure.
Vascular endothelial cells -> angiogenesis
Fibroblast produce new fibrous tissue to fill defects.
CELL CYCLE
A sequence of events controlling the proliferation of cells.
Key processes- DNA replication, mitosis.
A series of steps with checkpoints for accuracy of processes.
Checkpoints allow progression to the next stage if everything is correct.
G1 -> S -> G2 -> M
CELL TYPES
Most tissues contain variable proportions of continuously dividing cells, quiescent cells which are non dividing, but can return to the cell cycle, and non dividing cells.
3 TYPES OF TISSUE
- LABILE
- STABLE
- PERMANENT
LABILE TISSUES
Continuously dividing- continuously lost and replaced.
Mature from stem cells and also proliferation of mature cells.
eg. HAEMATOPOETIC CELLS, SURFACE EPITHELIA (skin cells, GI tract epithelium, urinary tract urothelium)
STEM CELLS
Seen in continuously dividing tissues. eg in basal layer of epidermis, turn in to TA (transit amplifying) cells.
Are replaced by differentiated cells, which are generated from stem cells.
There is an equilibrium between this and death of mature cells.
SELF RENEWAL CAPACITY.
ASYMMETRIC REPLICATION- every time the stem cell replicates, one daughter cell becomes more specialised, while the other remains undifferentiated.
SKIN STEM CELLS
Seen in the epidermal base layer.
Primary site is hair follice ‘bulge’.
Can generate follicles and epidermis.
Skin stem cells are slow cycling and only divide (asymmetrically) 4-6 times per year.
Rapidly dividing progenitor (TA) cells take care of daily maintenance, but only have a small, short lived response to wounds.
If a wound occurs, the stem cells will make a GREATER, MORE SUSTAINED contribution.
DIGESTIVE TRACT STEM CELLS
Digestive tract stem cells produce:
-PANETH CELLS- One of the principal cell types in the GI tract. Support stem cells and have granules which can secrete defensins and other products (lysosymes etc)
- NEUROENDOCRINE CELLS- Secrete hormones in response to neural input.
- GOBLET CELLS- Produce mucous.
- ENTEROCYTES- Main cells making up the GI epithelium.
- M CELLS- Microfold cells, transport particles/molecules from the gut wall to immune cells across the mucosal barrier. Important in stimulating mucosal immunity.
EMBRYONIC STEM CELLS
PLURIPOTENT- can make any cell type.
ADULT STEM CELLS
Haematopoietic, mesenchymal.
Small numbers are seen among differentiated cells in tissues and organs. Can make some or all of the cell types associated with that particular tissue or organ.
Mesenchymal stem cells are also found in tissues.
INDUCED PLURIPOTENT STEM CELLS (iPS)
Mature cells reprogrammed to make pluripotent stem cells.
Can now be done with almost 100% efficiency and in a synchronised manner.
Done by repressing protein Mbd3, which normally stops the pluripotency programme in cells as an embryo develops.
STABLE TISSUES
Quiescent, in G0 stage of cell cycle.
Not dividing currently, but can proliferate in response to injury.
PARENCHYMAL eg. liver, kidney, pancreas.
ENDOTHELIAL CELLS
FIBROBLASTS
SMOOTH MUSCLE CELLS.
Stable tissues have a limited capacity of regeneration.
RENAL TUBULAR REGENERATION
Nephrotoxins don’t normally damage basement membranes.
Ischaemia/infarct can and does damage basement membranes.
BM damage causes tubular atrophy and fibrosis.
There CAN be regeneration after ischaemia however, if there is reperfusion of the area.
Regeneration- Epithelial cells proliferate over basement membrane.
-Form a low cuboidal lining (rather than a mature columnar lining) within 3 days.
-Normal appearance by 7-14 days.
New cells are not identical to original cells, but there is eventual restitution of function.
LIVER REGENERATION
The liver can regenerate from as little as 25% of original parenchyma. eg. partial hepatectomy (surgical removal)
Adjusts to size of animal.
Hepatocytes show anisokaryosis and mitotic activity (mitotic figures are visible)
OVAL CELLS- Progeny liver specific stem cells.
Can differentiate in to hepatocytes or bile duct epithelial cells (cholangiocytes).
Oval cells are only identified when resident hepatocytes can’t enter the cell cycle.
PERMANENT TISSUES
Terminally differentiated and are NOT PROLIFERATIVE IN POSTNATAL LIFE.
eg. neurones, cardiac cells.
Their limited proliferative capacity is not sufficient for regeneration.
Skeletal muscle is permanent tissue, but satellite cells provide some regenerative capacity.
SKELETAL MUSCLE REGENERATION
Satellite cells are present between basal lamina and sarcolemma.
They are released by injury, activated, and enter the cell cycle.
The basal lamina MUST REMAIN INTACT to act as a scaffold (it can bridge a 2-3mm gap)
Satellite cells become MYOBLASTS and fuse end to end, forming myotubes, which then mature, with nuclei becoming peripheral.
If the basal lamina is disrupted, the myoblasts trying to proliferate will form muscle giant cells.
Seen in trauma, infarction, bacterial infection.
Satellite cells may be killed.
CLINICAL USE OF STEM CELLS IN VETERINARY MEDICINE
Used in regenerative medicine- “replacing or regenerating cells, tissues or organs to restore or establish normal function”.
This may involve stimulation of the body’s own repair mechanisms.
REGENERATIVE MEDICINE METHODS
- Cell therapies- injection of stem cells or progenitor cells
- Biologically active molecules- injected alone or secreted from infused cells
- Tissue engineering- transplantation of tissues and organs grown in the lab (in vitro)
eg. SDFT therapy in racehorses.
