Stem Cells And Regenerative Medicine Flashcards
What are the sources of stem cells?
Induced pluripotent
Embryonic
Adult
How do you create iPSCs?
Take any cell and expose it to specific plutipotency factors
What are the specific pluripotency factors?
Oct 4, sox2, KLF4 and Cmyp
Why are iPSCs used?
To replace lost tissue - good because the cells are from the patient so it reduces risk of rejection
What type of stem cells are embryonic stem cells?
Pluripotent
Where are embryonic stem cells taken from?
Blastocyst
What can embryonic stem cells form?
Any tissue from the three layers of the inner cell mass
What type of stem cell are adult stem cells?
Multipotent
How do you use adult stem cells?
Amplify in vitro
What can stem cells be used for?
Drug screening Disease modelling Developmental biology 3D organoid models Cell differentiation Model for basic and translational studies Cell replacement therapy
Where are tissue-specific stem cells maintained?
Stem cell niches
What is the method for iPSC creation?
C-Myc promotes DNA replication and relaxes chromatin structure
- > allows oct 3/4 to access its target genes
- > Sox 2 and KLF4 also cooperate with oct 3/4 to activate genes
- > encode transcription factors which establish the pluripotent transcription factor network
- > results in the activation of epigenetic processes that establish the pluripotent transcription factor network
IPSCs have a similar global gene expression profile to which other type of stem cells?
Embryonic
Why are stem cells used in CV disease?
Post heart attack, there is lots of cardiac muscle death, fibrosis and scarring - so SCs are used to replace this
What are the cardiac regeneration strategies used in CV disease?
Cell transplantation to replenish lost cardiomyocytes
Stimulation of endogenous cardiomyocytes
Neovascularisation
Why is neovascularisation a good thing in CV disease?
Improved circulation to injured area
Paracrine effects improving CM replacement
What are the challenges of transplanting cells to promote cardiac regeneration?
Immune rejection
Manufacture/ isolation of sufficient cells
Mode of delivery and clinical regulation
What is the immune response in neonatal mouse hearts?
Embryonic macrophage infiltration
Revascularisation
Global cardimyocyte proliferation
What is the immune response in neonatal mouse hearts?
Embryonic macrophage infiltration
Revascularisaion
Global cardiomyocyte proliferation
What is the immune response in adult mouse hearts?
Monocyte macrophage infiltration
Limited revascularisation
No cardiomyocyte proliferation
What is the normal lymphatic response to a heart attack?
Doesnt clear excess fluid, which leads to oedema and inflammation
What happens to the lymphatic response to a heart attack if the lymphatic system is stimulated with a modified form of VEGFC?
Improves the clearance of fluid which improves cardiac repair and function
What is an issue with iPSC cardiomyocytes?
Spontaneously depolarise faster than normal cardiomycytes so can cause tachycardia
What is myocardial thymosin beta 4 nessecary for?
Epicardial migration, coronary vasculature and cardiomyocyte survival
What can myocardial thymosin beta 4 addition to adult hearts cause?
Stimulation of epicardial outgrowth and neovascularisation
What does reexpression of wt1 give rise to?
Cardiac progenitors in the MI injured adult heart
What can cardiac progenitors in the MI injured adult heart differentiate into?
De novo cardiomyocytes
How is stem cell therapy used in cancer treatment?
After chemo/radio, SCs can be used to reconstitute healthy cells
What do MSCs do in cancer treatment?
Deliver genes, nanoparticles and oncolytic viruses to cellular niches due to intrinsic tropisms
What can exomes of MSCs and NSCs do?
Target the drug to tumour sites
What can stem cells be used for in burn treatment?
Replace lost skin cell types,
Speeding up endogenous healing
Generate ECM and produce paracrine signals which aid healing
What are fetal fibroblasts formed from?
ESCs
Why can fetal fibroblasts improve skin repair?
Improve skin repair due to high expansion ability
Low immunogenicity
Intense secretion of bioactive substances
What bioactive substances do fetal fibroblasts secrete?
VEGfs, REFs and fGfs
Why are epidermal stem cells good for burn treatment?
High proliferation rate
Easy access
Keep their potency and differentiation potential for long periods
Generate most stem cell types for repair and regeneration
Why are mesenchymal stem cells good for burn treatment?
High differentiation potential
Certain degree of plasticity
What can iPSCs be differentiated into to be used in burn treatment?
Dermal fibroblasts, keratinocytes and melanocytes
How does using stem cells in burns treatment work?
Cell isolation and purification
Cell and tissue assembly
Delivery
How can stem cell derived tissues be delivered?
Spray, dressing or 3D printing of cell sheets
What are responsible for replacing damaged corneal cells and where are they found?
Limbal stem cells at the edge of the cornea
What happens if the limbal stem cells are lost?
The cornea can’t be repaired -> affects the light entering the eye -> vision loss
How does limbal stem cell transplant work?
They are collected from a healthy part of the eye, expanded in the lab and then transplanted
What does a limbal cell transplant do?
Repairs the cornea and permenantly restores vision
What are some limitations of limbal stem cell transplant?
Only works if the patient has a healthy section of limbus from which to collect the LSCs from
What is retinal pigment epithelium?
Single layer of post mitotic cells that are a barrier to the photoreceptor layer
What can the retinal pigement epithelium cells be damaged in?
Age-related macular degeneration, retinitis pigmentosa and lebers congenital anemosis
What type of stem cells can you make retinal pigment epithelium from?
ESC and iPSC
