everything Flashcards
HSC intrinsic factors necessary for normal HSC maintenance in vivo
Tie1/2 - RTKs that promote HSC quiescence
CXCR4/SDF-1R Notch - GPCR that keeps HSC in niche
Hoxb4/4/c4/d4 - TFs that promote self renewal
HSC extrinsic factors that are necessary for normal HSC maintenance in vivo
angiopoietin - LOF results in defects in post natal HSCs - binds Tie1/2
CXCL12/SDF-1 - ligand for CXCR4 - produced by niche reticular cells
detal-like/Jagged - notch ligand in HSC niche cells
age related changes in HSC
pro-inflammatory signalling - higher activation of NF-kb pathway
increased ROS - DNA damage and increased p38 kinase activity
telomere shortening - p15INK4A activation and differentiation/senescence
changes to chromatin (hitone acetylation)
changes to niche factors - ECM composition + stiffness, fewer osteoblasts, increased adiposcytes..
HSC transplants helping brain
supplementation w youthful factors
depletion of aging factors
decreased reactive microglia
decreased synapse loss
increased cognitive function
autologous vs allogenic transplant uses
autologous:
- patients with myeloma (cancer of plasma cells)
- bm taken from patient in remission
problem: re-infused bone marrow may still contain cancer stem cells
allogenic:
- patients with chronic myeloid leukemia
problem: any HLA mis-match results in reection and graft vs host disease
fact: identical match btwn siblings probability = 25%
95% of autologous and 25% of allogenic transplants now performed using mobilized peripheral blood
graft v host disease facts
acute GVHD = within first 3 months - due to T cells in donor transplant material
chronic GVHD = after 3 months - likely to be result of T cells differentiating out from stem cells in graft
cord blood as a source of haematopoietic sc for transplantion how do we feel
advantages:
- work well across HLA mismatches
- few problems w viruses
- decreased occurence of gvhd
- readily available
disadvantages:
- low numbers of cells
- 20k cells/kg of patient weight (eliminates ~80% of adults)
- delayed engraftment
- delayed immune reconstitution
engraftment success = correlates with # of CD34+ cells used
best combo of cytokin cocktail
stem cell factor
thrombopoetin
flt-3 ligand
- increased no. of CD34+ cells
- increased reconstitution of SCID mouse assays
(severe combined immunodeficient mice = will accept growth of human stem cells)
some active clinical trials of stem cell
nov 2023
261 musculoskeletal diseases
209 chronic gvhd
204 respiratory tract diseases
4 things that decrease w age:
- ____ #
- _____ #
- mean _______ length
- total _________
MSC
CFU-F
telomere
population doublings
MSCs secrete enzymes (____ and ____) which promote _____ of ____ from M1 to M2 (M1 and M2 mean what respectively)
COX2
IDO
repolarization
macrophages
M2 macrophages prevent ______ whilst inducing ____ cells
neutrophil invasion and t-cell stimulation
treg
in the dermal layer of the skin - mostly collagen, the cells are mostly what
fibreblasts
epidermis
dermis
hypodermis
composition
keratinocytes - adhere to each other and basement membrane very tihgtly, form the protective barrier
epithelial layer
fibroblasts - main mesenchymal component, produce collagen, endothelial cells - form the vasculatorue
mesenchymal layer
adipocytes - NRG storage, thermal regulation, niche for immune cells and MSCs
factors involved in the morphogenesis of hair follicles
BMP/TGF beta signalling from epidermis to demis is required for hair follicle formation
wnt signalling from dermis to epidermis is required for correct spacing of follicles
_____ = crucial for stratification of skin which occurs during embryonic development
P63
epidermis has 3 SC niches
- bulge region of hair follicle
- basal layer of interfollicular epidermis
- sebaceous gland of hair follicle
in neonatal mice, the ____ repopulate the epidermis, but difference in adult mice:
bulge SC
adult mice: only happens in response to injury
bulge activation hypothesis
death of the lower part of the follicle (catagen) brings the dermal papilla close to the stem cells in the bulge
dermal papilla activates stem cells to restart hair growth (anagen)
when hair cell shrinks, it brings it closer to the bulge cells - which then activate the bulge stem cells through WNT signalling
if you have high lvls of BMP, it can do what
inhibit hair follicle activation
bUT if there’s enough WNT it can counteract this
WNT signalling from DP stabilizes what - and leads to what
beta catenin - leads to gene expression changes that activate bulge stem cells during the hair cycle - this is needed to counteract bMP inhibitory effect on bulge SC
_____ inhibits _____ signalling
numb
notch
notch signalling promotes what
differentiation
white blood cells
stem/progenitor cells
mesenchymal stem cells
function
positive role as well as negtive - prevent infection, stimulate neovascularization, esxcessive inflammation - chronic wound envroinment
stimulate healing, suppress inflammation
stimualte healing, suppress inflammation
