10. tissue repair Flashcards
tissue turnover
maintaining tissue architecture and function during progressive aging and constant changes in demand
tissue repair
restoration of tissue architecture and function after damage
repair repeats morphogenesis
what happens up to 28th week of of embryo
no scarring and inflammation during repair
the key process in adult tissue turnover and repair
inflammation
it is a homeostatic process
tissue maintenance and immune defence are part of the same process
stem cell niche
microenvironment of a stem cell a spatial structure in which stem cells are housed and maintained allowing self-renewal in the absence of differentiation
what does stem cell division give rise to
transit amplifying cells
= daughter cells comitted to differentiation
undergo clonal expansion
one stem cell becomes dormant after division
what is the fate of cells regulated by
what are the different types of these
external signals- cross talk with other cells and ECM (microenvironment)
juxtacrine signalling- between tissues
paracrine signalling- exchange signals
endocrine signalling- blood
what is the factor that determines cell differentiation
the plane of cell division
what controls the differentiation of epidermis
The fate of the daughter cells is controlled
interactions with the basement membrane
signals from neighbouringcells
- Activation of the Wnt pathway inhibits the switch from stem cell to TA cell
- Notch signaling in a stem cell inhibits adjacent cells from staying stem cells.
classification of cell death
morphological appearance (apoptotic, necrotic, autophagicor mitosis-associated)
enzymological criteria (w/ and w/o the involvement of nucleases or proteases, such as caspases, calpains, cathepsinsand transglutaminases)
functional aspects (programmed vs. accidental, physiological vs. pathological)
immunological characteristics (immunogenic vs. non-immunogenic).
which protein is involved in recognition of cells that are damaged beyond repair?
phosphatidylserine- direct binding of phagocyte with apoptotic cell
indirect binding via bridging proteins
three groups of tissues
Liable: bone marrow, skin, GI epithelium)
- continuously renewing
- can easily regenerate after injury
Stable: (e.g. liver, kidney, pancreas)
- conditionally renewing
- limited ability to regenerate (except liver!)
- normally in G0, but can proliferate if injured
Permanent:
(e. g. neurons, cardiac muscle)
- static or non-proliferative
- cannot regenerate
(injury always leads to scar)
what type of stem cells are adult stem cells
mostly multipotent, some pluripotent
two ways of tissue repair
what are the phases
regeneration
replacement: tissue replaced by scar= non functioning connective tissue
can be both
Inflammation hours –days
Restricting damage
- Debridement
- Antimicrobial defence
Proliferation days –weeks
Producing replacement
- Specific cells
- Specific matrix
Maturation weeks –months/years
Restoring function
•Functional remodeling
regeneration in bones, liver, NS, and skin
Bone full regenerative capacity for all tissues involved
Liver tissue dependent parenchyma regenerates if mesenchyme intact, if not scarring
ECM must still be intact
Nervous system
PNS: regeneration possible (proximal grows back to repair distal)
CNS:always scarring, leads to astrogliosis
Skin layer dependent epidermis = regeneration
dermis & hypodermis= scarring
wound healing in epidermis and dermis
epidermis:
- adjacent keratinocytes“leap-frog” along collagen fibresuntil they meet
- if gap is too wide, they stop
- when they meet, they form a sheet and cover the denuded area
dermis:
- Endothelial cells follow laminin fibresuntil they meet and fuse
- if gap is too wide, the capillary sprouts turn sideways
- critical wound size about 2-3cm
first intention wound healing
small wounds
narrow margins
regeneration >> fibrosis
healing is fast;
minimal scarring
second intention wound healing
larger wounds
wide margins
fibrosis >> regeneration
healing is slower;
more scarring
inevitable infection
Large burns and ulcers
wound closure
aim to initiate 1st intention healing
suture removal depends on location
stitch, staple, glue, tape
wound management
wound covers
must be clean
larvae therapy
skin mesh, enginereed epidermal sheets and skin substitutes to cover large or non healing wounds
wound remodelling
