Regenerative biology Flashcards
What is regenerative biology?
Regeneration is the ability of organisms to restore their structures in form and function
Aquatic vertebrates have more regenerative capabilities than terrestrial vertebrates
Simple organisms have remarkable ability to whole body regeneration such as hydra, starfish and planaria
Morphallaxis Vs epimorphosis
Hydra use morphallaxis
Salamander limbs use epimorphosis
Imagine a rectangular French flag is a worm with its head at left blue end and tail at right red end
Epimorphosis involves growth where as morphallaxis is a change of cell fate
If you were to remove the left half of the French flag with morphallaxis you would then get a new French flag that is the size of the half as it changed pre existing cell fates
With epimorphosis it simple regrows the missing half so you go back to having a French flag of the same size
Wounding causes an immediate wound response
Early wound signals:
- ATP released by damaged cells
- Intracellular calcium is elevated
- Reactive oxygen (H2O2) is released
These molecules act as signals in first few minutes to initiate wound response
The wound response:
1. Causes cytoskeletal changes to close the wound. The cell on the edge will form “Purse strings” to close the wound if its small enough
2. recruits immune cells to the site
3. Initiates regeneration or scar formation
How does wounding initiate regeneration?
Damage -> wound response which either -> regeneration or -> scarring
Fibrosis (scarring) is permanent and caused when fibroblasts secrete high levels of extracellular matrix (Collagens etc)
Salamander regeneration
When you amputate the limb it send out early wound signals
The wound closes, cytoskeletal rearrangements and epithelial movement
The would epithelium forms and signals from it induce dedifferentiation
The the blastema forms and blastemal cells proliferate and then regrowth beings
Wound epithelium is thicker than surrounding skin and is know to secrete signals. The formation of wound epithelium is first sign that regeneration has begun
Wound epithelium is similar to AER and blastema is similar to progress zone
Regeneration recapitulates development
The blastema is formed by cells that dedifferentiate (partially)
Multipotent blastema cells will form undifferentiated blastema cell and then that one cell type will form what ever is needed
With lineage-restricted blastema cells only cartilage would be able to form cartilage blastema cells (a proliferative cell) and then a cartilage cell in the regenerated limb
see diagrams
Planaria (a very small flatworm)
The minimum size of fragment that can regenerate is 1/279th (0.3%)
Neoblasts are adult stem cell of Planaria and are scattered throughout animal
Head regeneration involves epimorphosis
regeneration from small fragments results in small animals - morphallaxis
Some neoblasts are pluripotent, others are lineage restricted
Hydra
Simple animal with two germ layers and adult stem cells called interstitial cells
They are continually growing due to interstitial cells and reproduce by budding
Cell division and interstitial cells not required for regeneration - morphallaxis
WNT signals from hypostome are able to induce bud formation
Zebrafish heart
If 20% ventricle of adult zebrafish is removed it will regrow
Wounding causes activation of epicardium - thin layer cells that encapsulates the heart
Activated epicardium secretes retinoic acid, IGF2 and hedgehog signals
Cardiomyocytes (muscle cells) de-differentiate and proliferate at wound site
Vascularisation takes place and regenerated cardiomyocytes becomes active
Human regeneration
Skeleton has lots of regenerative potential but limits as you get older
Bines reheal after breaking
Skin has lots of stem cells in and often regrows, e.g. cuts
Adult liver can regenerate even after a lot of damage
Muscle cells often regenerate
Development and regeneration use the same set of genes
This suggests that mammals could regenerate if scientists could figure out how to activate the regeneration program
Could we harness the power of endogenous regenerative mechanisms?
BMP2 soaked beads induce skeletal regeneration from digit and limb amputations
Experiments currently being done on mice
