What is meant by regeneration?
The replacement of damaged cells by functional, differentiated cells (arising from stem cells).
In terms of replication, cells (and therefore tissues) can be categorised. What are these categories and give examples of tissues which fit into each category.
Labile - these cells can continue to replicate throughout life. Eg epidermis of the skin, transitional epithelium of the urinary tract.
Stabile - these cells are in G0 of the cell cycle, but under stimulus they can be forced to enter G1 of the cell cycle and proliferate. Most of the time they are quiescent. Eg, the liver, kidney. Stem cells and differentiated cells are both involved in the proliferation.
Permanent - these cells are unable to proliferate at all. They contain some stem cells however these stem cells are unable to mount an effective response and so they cannot proliferate. Eg, the heart, neurones, skeletal muscle.
What is special about the progeny of stem cells? What is this called?
One daughter cells goes on to differentiate whereas on remains as a stem cell.
What is meant by unipotent, multipotent and totipotent? What cells are these terms referring to?
All 3 refer to stem cells.
Unipotent- the stem cell gives rise to one type of adult cells.
Multipotent - the stem cell gives rise to many types of adult cells (eg haematopoeitic stem cells, HSC)
Totipotent - this refers to embryonic stem cells, which can give rise to all tissues of the body.
If the collagen framework is damaged, what type of healing occurs? Regeneration or fibrous/scarring?
Fibrous and then scarring
Name the 3 key components of fibrous repair.
Briefly describe the 3 components of fibrous repair.
Inflammatory cells - eg macrophages - these phagocytose debris
Endothelial cells - required for angiogenesis - this is vital.
Fibroblasts - lay down collagen as well as contracting (myofibroblasts)
This is induced via VEGF and vital as it supplies a route for oxygen delivery as well as nutrients for growth and repair and inflammatory cells.
Endothelial proteolysis of basement membrane, after which endothelial cells migrate via chemotaxis and then proliferate. These endothelial cells then mature, and vascular remodelling occurs. Peri endothelial cells are then recruited.
Initially the granulation tissue is highly vascularised, but as the process carries on, it becomes less vascularised and the wound heals into a fibrous scar, which matures and shrinks (myofibroblasts).
Separates the tissue out into compartments and also supports the cell as well as anchoring it. It facilitates cell migration. Collagen is the most abundant protein and is vital for the framework of the fibrous repair.
Which type of collagen is most abundant in the body? Which amino acid is at every 3rd space?
Type I collagen.
What is vital for regeneration of damaged cells?
An intact connective tissue scaffold. This is an absolute must.
Outline the synthesis of collagen
Synthesis of preprocollagen on ribosome.
Entry into RER.
Signal sequence cleaved by signal peptidase(RER)
Hydroxylation of proline and lysine residues by Prolyl Hydroxylase (needs vitamin C. Hence scurvy sees a defective helix) (RER)
N-linked oligosaccharide are added. (RER)
Chain alignment and disulphide bond formation. (RER)
Formation of procollagen (RER)
O-linked oligosaccharides added (Golgi)
Packaged into vesicles and exocytosed. Cleaved into tropocollagen. (Ehlers Danlos is defective conversion into tropocollagen).
Cross linking of tropocollagen via Lysyl oxidase (Vitamin B6 needed)
Briefly explain contact inhibition.
Normally when cells are isolated from the rest, they will continue to grow and proliferate until they make contact with a neighbouring cell. They then stop growing.
Besides contact inhibition, what other control of regeneration and repair exists?
Autocrine, paracrine and endocrine.
Growth factors - coded for by proto oncogenes and they can stimulate or inhibit cell proliferation. Eg VEGF PDGF TNF Epidermal GF
Outline healing by primary intentions.
This occurs in wounds when there is clearly apposed edges - eg with a scalpel incision.
There is minimal clot and granulation tissue formation, and there is minimal contraction and scarring.
There is a risk of trapping bacteria, in which case an abscess can form.
Outline healing by secondary intention.
This occurs when the edges of the wound are not apposed.
There is considerably more scarring, wound contraction and granulation tissue.
Takes longer than primary intention and the scar tends to be bigger.
Occurs in ulcers, abscesses, infarcts etc.
Outline the process of bone healing.
1) Haematoma formation. Bone cells at the edge of the break die due to avascular necrosis. Osteoclasts begin to remove the dead and damaged tissue, with macrophages eventually removing the clots.
2) Blood vessels infiltrate and granulation tissue (tissue full of capillaries and fibroblasts) develop. Fibroblasts lay down collagen that spans the break and some differentiate into chondroblasts and lay down hyaline cartilage. A fibrocartilaginous splint forms. Osteoblasts from nearby periosteum infiltrate and lay down bone.
3) More bone is laid down and the callus is replaced by bone. Endochondral ossification will eventually replace all cartilage with bone. Some intramembranous ossification also occurs and so new bone is laid.
4) the bone is remodelled according to mechanical stresses and therefore appears as it did before the break.