9/ regenerative biology Flashcards
what sorts of vertebrates and other organisms have better regenerative capabilities
- aquatic
- can regrow limb, eye, spinal cord, heart
- simple organisms like planarian, hydra and starfish can regenerate the whole body (into 2 smaller bodies)
morphallaxis vs epimorphosis
- morphallaxis: used by hydra. If chopped in half, will regrow to full hydra w/o proliferation (can proliferate later). cells gain new identities - repatterned
- epimorphosis: used by salamander. limb closes over and forms clump of regenerative cells. reforms to appropriate size
early wound signals
- ATP released by damaged cells
- elevated intracellular calcium
- reactive oxygen H202 (peroxide) released
- these initiate wound response over few mins
wound response
- cytoskeletal changes to close wound - cells on edge form purse strings to close wound if its small enough
- recruits immune cells to site
- initiates regeneration or scar formation dep on regenerative capabilities
whats a keloid scar
raised scar on skin
what is fibrosis
- permanent scarring
- caused when fibroblasts secrete high levels of extracellular matrix like collagens
stages of salamander limb regeneration
- amputation. early wound signals
- wound closure. cytoskeletal rearrangements and epithelial movement
- signalling from wound epithelium (thicker than skin) to induce dedifferation
- blastemal cells proliferate and regrowth begins
- blastemal cells are underneath the wound epithelium
2 hypotheses for blastema formation
- multipotent blastema cells: dedifferentiate into multipotent state then can differentiate into multiple tissues
- lineage-restricted blastema cells: dedifferentiate and proliferate and migrate but still fixed in their fate (muscle to muscle etc)
out of dermis, cartilage, muscle, schwann cells and epidermis, all cells can dedifferentiate but only which 2 can transdifferentiate into each other?
dermis and cartilage
planaria regeneration
- simple organism that looks wormy
- 0.3% is able to regrow
- neoblasts are the adult stem cells of planaria and are scattered throughout - some are pluripotent, others lineage restricted
- head regeneration involves epimorphosis - forms blastema
- regeneration from small fragments results in small animals - morphallaxis
what is a hydra, how does it reproduce?
- simple animal with 2 germ layers and adult stem cells called interstitial cells
- continually growing due to interstitial cells and reproduce by budding (morphallaxis, don’t use stem cells)
zebrafish heart regeneration
- if 20% of ventricle of adult zebrafish is removed it will regrow
- wound causes activation of epicardium (layer of cells around heart)
- activated epicardium secretes retinoic acid, IGF2 and hedgehog signals - regeneration signals
- cardiomyocytes dedifferentiate and proliferate at wound site
- vascularisation takes place and regenerated cardiomyocytes become active
human regeneration - name organs/tissue
- bone
- skin - basal keratinocytes
- muscle - satellite cells
- liver
what suggests mammals could regenerate if scientists could figure out how to activate regen program?
regenerative animals reuse genes they used during initial development. if we reactivate these pathways?
BMP2 soaked beads experiment - aims and what happened?
- harness power of endogenous regen mechanisms
- induce skeletal regen from digit and limb amputations
- BMPs ligand important in skeletal development
- did result in some regen
- idea there will be multiple signaling molecules - have to apply dif at dif times
