stem cells Flashcards
what is the effect of aging on the stem cell niche?
aged stem cell niche fails to send proper signals to stem cells
TGF beta levels increase and impairs the functions of satellite cells
FGF2 signalling impairs cell renewal
results in changes in cell fate decisions
how do you culture stem cells in vitro?
embryonic cells are grown on a layer of fibroblast feeder cells
this provides a stem cell niche in vitro
provides the factors which supress differentiation or promotes self renewal
removes the toxic or inhibitory factors from the growth medium
contains leukaemia inhibitory factor which drives the transcription of stem cell genes
what are induced pluripotent stem cells?
behave like embryonic stem cells through genetic reprogramming
which transcription factors are required for cell self renewal?
octomer transcription factor 2/4
Nanog
Sox 2
these are known as OSKM or Yamanaka factors
how are transcription factors needed for self renewal transduced into induced pluripotent cells?
by lentiviral or retroviral transduction of an OSKM overexpression plasmid and CRISPR knockout of p53/p21
integrates the genes into the host
induction of OSKM factors increases proliferation capacity and differentiation potential
what are autologous stem cell therapies?
therapies using the patients own stem cells
eg mesenchymal cells for cartilage repair
what are allogeneic stem cell therapies?
therapies which use a donors stem cells
the idea is to generate an off the shelf cell therapy which can be used for any patient
which stem cells are known to supress/evade the immune response?
mesenchymal stem cells
what can mesenchymal stem cells differentiate into?
bone
cartilage
adipose tissue
what are the pros of autologous therapies?
available for most patients
no need for matched donors
partial graft may be beneficial
what are the cons of autologous therapies?
my need 100% gene modification
viral reservoirs are reduced but not eliminated
likely requires a combination of therapies q
what are the pros of allogeneic therapies?
complete replacement of host cells with donor cells
potential elimination of viral reservoirs
may not require genetic modification
what are the cons of allogeneic therapies?
need for a matched donor
100% donor chimerism may be required
greater chance of mortality due to immunosuppressive therapy
what are common cons of autologous and allogeneic therpaies?
costs are considerably high
not feasible in resource limited settings
both have associated mortalities
what are scaffold based therapies?
uses cellular stem cell therapy in conjunction with a scaffold
scaffolds can be bioactive or inert
what is a hydrogel scaffold?
a cross linked hydrophillic network which swells upon exposure to water
it is much like the naturally occurring ECM
they are often modified to incorporate drug delivery systems which enhance the survival and differentiation of the stem cells seeded inside
what are hydrogel scaffolds used to treat?
tendon repair
kidney damage
neural regeneration
what are electrospun scaffolds?
high voltage field applied to polymer solution which draws out thin fibres
promotes stem cell culture and differentiation into tissues
cells can be seeded onto the scaffold or bioactive molecules
what is stimulation of endogenous repair?
use of biomaterials to stimulate stem cell niches in order to achieve tissue repair
how is platelet rich plasma used to treat injuries?
blood is taken and centrifuged to get platelets which can be reinjected into injury sight
typically autologous
causes upregulation of proliferative and survival pathways ERK’s and AKT
can promote recruitment of neutrophils and macrophages
what is macrophage-mediated debris clearance?
microglia clear cell debris and facilitate reorganization and repair
strong link with regeneration in the central nervous system
insufficient clearance is linked with neurodegenerative diseases and aging
does endogenous repair have memory?
data suggests inflammation can trigger epigenetic memory of injury
if inflamed skin is wounded, heals and is re wounded, the second wound heals more rapidly
