stem cells and regenerative medicine

Question 1

what are stem cells

Answer 1

differentiate into Manu cell types

self renewal

provide new cells

several types

targeted by researchers for their therapeutic potentials

Question 2

stem cells and disease

Answer 2

blindness
wound healing
spinal cord Injury
cancers

Question 3

stem cell sources

Answer 3

embryonic stem cells

induced pluripotent cells

adult stem cells

uses:
model for basic and translational studies 
disease modelling 
drug screening 
cell replacement 
cell differentiation 
3d organoid models 
developmental biology

Question 4

comparison of stem cell types - tissue specific

Answer 4

tissue specific stem cells maintained in special supportive microenvironemnts called stem cell niches

• supporting ECM
• neighbouring niche cells
• secreted soluble signalling factors
• physical parameters: stress, tissue stiffness
• environmental signals

Question 5

generating iPSC cells

Answer 5

c-Myc promotes DNA replication and relaxes chromatin structure

allows oct3/4 to access target genes

sox2 and klf4 cooperate with oct3/4 to activate target genes

these encode TF’s which establish pluripotent TF network

results in activation of epigenetic processes that establish the pluripotent epigenome

these cels have a similar global gene expression profile to that of ES cells

Question 6

describe stem cell tracking

Answer 6

in vivo imaging can aid the development and clinical translation of cell based therapeutics using non-invasive in vivo long term cell tracking in the preclinical and clinical settings

Question 7

cv disease and regeneration

Answer 7

neonatal hearts = embryonic macrophages

adults = monocytes macrophages

lymphatic response = oedema and inflammation. if stimulated with IGFC = increased lymphatic response = reduces oedema and inflammation

Question 8

making cardiac lineages from ipsc cells

Answer 8

at forefront of cardiac regenerative investigation

IPSCs are specified towards pre cardiac mesoderm by inhibition of glycogen kinase 3b = downstream switch for a number of signalling pathways,, incl WNRT signalling = differentiation of cardiac progenitor cells

Question 9

stem cell therapy in treatment of cancer

Answer 9

chemo/radiotherapy kills cancerous cells

clinical trials for other tumour types, brain and Breast cancers, neuroblastoma, sarcoma

effector immune cells from ipsc/esc’s

production of anticancer vaccines

MSCs/NSCs deliver genes, nanoparticles, and ocolytic viruses to tumour niche due to intrinsic tumour tropism

exosomes extracted from the culture of drug priming MSCs/NSCs can target the drugs to tumour sites

mutation correction In vitro, drug testing in vitro before replacement in vivo.

Question 10

stem cell therapy for burns

Answer 10

fetal fibroblasts = improve skin repair due tp high expansion ability, low immunogenicity, intense secretion of bioactive substances such as FGF, VEG and KGF

epidermal stem cells = high proliferation rate and easy access and keep their potency and differentiation potential for Long periods. generate most skin cell types for repair and regeneration

mesenchymal stem cells = have high differentiation potential and certain degree of plasticity. migrate to injured tissues, differentiate and regulate tissue regeneration by production of growth factors, cytokines and chemokine

ipsc’s = can be differentiated into dermal fibroblasts, keratinocytes and melanocytes

Question 11

stem cell therapy for eye injury/disease

Answer 11

stem cells at edge of cornea, gimbal stem cells are responsible for making new corneal cells to replace damaged ones

if these stem cells are lost due to injury or disease, cornea can no longer be repaired. this affects ability of light to enter the eye, resulting in a significant loss of vision.

limbal stem cells are collected from adequately healthy donor eye, are expanded in the lab to sufficient numbers and transplanted into the damaged eye.

repairs the cornea and permanently restores vision

to avoid immune rejection,, treatment only works if patient has healthy section of limbus to collect limbus stem cells

IPSC cells can be induced to make corneal epithelial cells for transplant and exposure to right signals can transfer fibroblast cells into limbal stem cells

Question 12

eye injury pt 2

Answer 12

retinal pigment epithelium is a single layer post mitotic cells acting as a selective barrier to and a vegetive regulator of the overlying photoreceptor layer

RPE has a key role in retina maintenance and parts of the retina can die without a functional RPE leading to loss of vision

RPE cells can be damaged in a variety of diseases: retinitis pigments and leber’s congenital neurosis

RPE cells have been made from both ESC and Ipsc

Several clinical trials for diseases incl age related macular degeneration, retinas pigments and levers congenital neurosis show promise

Question 13

spinal injury treatment

Answer 13

neural/stem cell progenitor cell grafts can integrate into sites of spinal cord injury and generate neuronal relays across lesions that can provide functional benefit

calcium imaging of NSPC grafts in SCI sites in vivo and in adult spinal cord slices showed NSPC grafts organise into localised and spontaneously active synaptic networks

ontogenetic stimulation of host axons produced neuronal response in graft and vice Versa

in vivo imaging revealed that behavioural stimulation also elicited focal synaptic responses within grafts

thus neural progenitor grafts can form functional synaptic subnetworks whose activity patterns resemble intact spinal cord