Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Neuroscience > Regeneration (Stem Cells) > Flashcards

Regeneration (Stem Cells) Flashcards

1
Q

Features of NSCs

How can they be derived from MSCs

A

Differentiate into neurons, astrocytes, oligodendrocytes

Can be derived from MSCs in EGF/bFGF conditional medium through SOX1 activation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Development of NSCs from ESCs

A

ESC
Preliminary NSC
NSC (FGF/EGF responsive)
Definitive ESC

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

How does proliferation change with progression through development

A

Proliferation/cell turnover increases with increased specialisation

A slower turnover is associated with cell health and telomere length

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Main neurogenic niches

A

Subventricular Zone
Subgranular Zone of Dentate gyrus
Central Canal zone of SC

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Differentiation of NSCs

A

ChIP-quantitative PCR: HDAC2/3 bind genes associated with development/differentiation e.. Cebpb, Hoxd4, Ovol2, Zfp7

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Contribution of factors neuron development

A

Secretory factors control dorso-ventral, rostro-caudal differentiation

Forebrain: alpha-BMP, Wnt
Midbrain: FGF8
Spinal Cord: RA

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Inputs involved in purkinje cell differentiation

A

Balance of pro and inhibitory signals:
Fgf2
ROCK, TGFbeta (inhibitory)

Granule cells impact maturation/ development of a full phenotype

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

NSCs in hypoxic-ischaemic stroke

A

Hypoxic-Ischaemic stroke assc. with microglial activation and tissue loss

Hypoxia inducbile factors (HIF1, WntBeta, Catenin, IFN-y) are key mediators of O2 dependent mechanism of NSC proliferation/differentiation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

NSCs in chronic hypoxia

A

Chronic hypoxia has less of an inflammatory response

Recovery impaired due to glial scar formation, vs capacity of progenitors

Increases in cell proliferation and glutamatergic progenitors expressing the transcription factor Tbr2 in the SVZ following a hypoxia insult

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Parkinsons Disease- features

A

Loss of dopaminergic neurons in the Substantia Nigra

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

NSCs in Parkinson’s disease

A

NSCs can stimulate de-differentiation of astrocytes, and release of exogenous GFs
Inhibition of microglia, slow PD progression by micro-environment modulation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Akerud 2001- GDNF effects in PD

A

Akerud 2001: GDNF-releasing NSCs grafted into a mouse 6-Hydroxydopamine model of PD, preventing DAergic neuron degeneration and reducing behavioural impairments

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Qiu 2017- transplanting mDA progenitors

A 
Transplantation and induction of mDA progenitors at 3 time points of differentiation caused increased PSA-NCAM labelling, and labelling of neuronal markers
Increased maturation (TH+ cells) and satisfactory behavioural functional recovery
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Manipulating endogenous SCs in SCI

Neurospheres

Corns 2015

A

Cells cultured from the CCZ proliferate in vitro in response to EGF and bFGF, forming neurospheres

PNU (and Donepezil) increasing EdU labelling in CCZ and GM/WM, with increased CL for PANQKI, HUCD, Sox2

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Manipulating endogenous SCs in the hippocampus

A

Donepezil increases survival of newborn neurons labelled with BrdU/EdU in vivo, increasing CL with MBP

Cholinergic signalling
Alzheimers- due to reduced cholinergic signalling due to Amyloid beta plaques binding alpha 7

Beta 2 KOs have significantly smaller dentate gyri than age-matched WTs

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What can CSCs differentiate into?

A

Cardiomyocytes
Endothelial Cells
Smooth Muscle Cells
Fibroblasts

17
Q

Potential applications of CSCs

A

Recovery from cardiac injury
Increasing cell senescence with age

BUT Discrepancies as to source, potential turnover of CSC populations

18
Q

Evidence for CSCs in recovery

Ellison 2013

A

Isoproterenol induced injury model (causes diffuse CM death without affecting tissue architecture)
-Cre Recombinase mice (YFP in ckit+ cells)

Showed:

  • Increased BrdU labelling which co-expressed ckit+ YFP
  • Increased expression of GATA4 and Nkx2.5 (early TFs of cardiac lineage)
  • High tropism for cardiac tissue when eCSCs injected into tail vein
  • Ablation of ckit+ eCSCs w/5FU caused cardiomyopathy, hypertrophy, and HF
  • Transplanted eCSCs isolated after regeneration retained SC properties in vivo
19
Q

Evidence against CSCs in recovery

Van Berio 2014

A

MI Model
-Numbers of ckit+ CMs after injury very low
Loss of kit gene completely prevented CM formation from ckit+ cells

20
Q

Age-dependent effects of CSCs

Jesty 2012

A

Neonatal infarction in ckit-GFP hearts:

  • Expansion of ckit cells
  • Increased Nkx2.5 expression
  • Partial infarct regeneration
  • Adoption of myogenic and vascular fates

Adult mice: Modest ckit induction, no change in Nkx2.5, adopted a vascular fate

21
Q

Optimising CSCs with Pim1 Kinase

A

Pim1 Kinase: enhances proliferation, metabolic activity, differentiation, preserves mitochondrial integrity

Pim1 manipulation in hCPCs isolated from LVAD implantation patients

  • Decreased population doubling time, increased proliferation rate, reduced staining for senescence assc. beta-galactosidase, elongation of telomere length
  • p53/p16 has opposite effects
22
Q

SCIPIO trial of CSCs

A

CSC treatment increased LVEF, reduced infarct size

Over 4 months, and increasingly over 12 months

23
Q

Tang 2010- effects of exogenous CSCs

A

Injection of CSC-eGFP showed low numbers, but increased BrdU labelling increased
- % of ckit+/BrdU+ cells increased even in those with no EGFP+ cells, suggesting a paracrine action

24
Q

CADUCEUS Trial

A

Cardiosphre derived cells reduced scar size and mass

  • Did not affect myogenesis- evidence of paracrine action
25
Q

Exosomes in paracrine activity of CSCs

A

Exosomes: nanovesicles shed from cells which can pass on markers of disease, and cell survival/generation

Exosome-treated hearts:

  • Improved LVEF, decreased hypertrophy, dilated cardiomyopathy
  • Lower cytokine levels

-Exosome release suppression abrogated CDC benefits

26
Q

Targetting the endogenous CSC secretome

A

Adult CMs co-cultured with ckit+ CSCs attentuated apoptosis and increased caspase 3, IGF-1 expression

27
Q

Using MSC secretome

A

RCT of hMSCs demonstrated their safety
Increased LVEF, reduced arrhythmias

MSCs and CSCs additive benefits

28
Q

Bone marrow-derived stem cells

A

Improvements in LVEF, end-systolic/diastolic volumes, reduced risk of death
-Benefits may last more than 12 months in acute MI

29
Q

How does aging affect stem cell niches

A

Changes in efficiency of regeneration (prolonged inflammatory/fibroblastic activity, reduced MSC activation)
-Changes in pro-senescence/quiescence signals e.g. STAT3

e.g. systemically conjoining mice impairs muscle regeneration in the young, but improves in aged mice

30
Q

What is Quiescence?

A

Cells temporarily leave the cell cycle to exist in a sustained G0 phase

Influenced by factors such as p21, p27

31
Q

What is senescence?

What is SASP

Evidence of effects of p16 (Baker 2016)

A

Permanent, but not irreversible removal of cells from the cell cycle
Influenced by DNA damage, telomere erosion (p53, p21), oncogene activation (p16)

SASP: Senescence Associated Secretory Phenotype- senescent cells which go on to secrete pro-inflammatory molecules e.g. Interleukins

Baker 2016: Selective apoptosis in p16 inkA cells (accumulate in the heart with age)
-Reduced cardiac hypertrophy, increased resistance to beta-adrenergic stress, extended lifespan

32
Q

How does senescence contribute to inhibitory signalling in SC niches?

A 
Inflammasome activation e.g. cytokine secretion
SASP
Exosome release
Mitochondrial dysfunction
DNA damage
Reactive Oxygen Species formation

Contribute to cell cycle arrest
Injury may exacerbate this in CSC niches, with CM death, scarring/ stromal infiltration, ECM stiffness

33
Q

How is TNF alpha involved in inhibitory signalling in SC niches?

A

May have an inhibitory effect on CSCs

  • TNFR1 KO: massive upregulation of Mef2c and increased proliferation following MI
  • TNFR2 KO: similar response in smooth muscle/ endothelial cells
  • Endogenous TNF: blunted Nestin downregulation and suppressed beta3 tubulin expression
34
Q

How does aging affect inhibitory signalling in SC niches?

A 
MuSCs isolated from aged mice implanted into young mice cannot rejuvenate an injury
Treated MuSCs (p16/Jak2-Stat3 inhibition) transplant into young and old mice leads to improved regeneration

Price 2014: JAK-STAT targets in 18m mice are expressed higher than younger mice
- JAK2-STAT3 KD/ pharmacological inhibition stimulated satellite stem cell division and enhanced repopulation ability

35
Q

Methods of manipulating the SC niche

A

Creating an in vitro niche
- Issues with increased generation of ROS

Manipulating niches
GF/ cytokine administration, engineered ECM, O2 gradient, electrical pacing, cyclic straining etc.
Hydrogels, decellularised ECMs, synthetic matrices

36
Q

Effects of Exercise on CSCs

A

High intensity exercise increased BrdU labelling of ckit+ CSCs and CMs in the LV of exercising animals

  • Increased IGF-1, TGF-beta 1 (implicated in myocardial hypetrophy)
  • Increased expression of Neuregulin 1, Periostin, BMP-10 (regulating hypertrophy/ myocyte replacement following injury)
37
Q

Effects of Exogenous Growth Factors on CSCs

A

IGF/HGF in pig infarction model

  • Dose-dependently activated ckit+ CSCs, increased myogenic differentiation and improved CM survival
  • Reduced fibrosis and CM reactive hypertrophy
  • Reduced infarct size, increased LVEF 2 months after MI
38
Q

Effects of MSC secretome on NSCs in PD model

A

Increased expression of beta-actin and TH

  • Drove increase in proliferation
  • Improved behavioural effects of PD (spatial learning ability, apomorphine induced rotational asymmetry)

Neuroscience (17 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions