Stem Cells And Regenerative Medicine Flashcards by Filzah Khan

What are the sources of stem cells?

Induced pluripotent
Embryonic
Adult

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How do you create iPSCs?

Take any cell and expose it to specific plutipotency factors

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What are the specific pluripotency factors?

Oct 4, sox2, KLF4 and Cmyp

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Why are iPSCs used?

To replace lost tissue - good because the cells are from the patient so it reduces risk of rejection

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What type of stem cells are embryonic stem cells?

Pluripotent

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Where are embryonic stem cells taken from?

Blastocyst

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What can embryonic stem cells form?

Any tissue from the three layers of the inner cell mass

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What type of stem cell are adult stem cells?

Multipotent

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How do you use adult stem cells?

Amplify in vitro

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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

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Where are tissue-specific stem cells maintained?

Stem cell niches

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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

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IPSCs have a similar global gene expression profile to which other type of stem cells?

Embryonic

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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

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What are the cardiac regeneration strategies used in CV disease?

Cell transplantation to replenish lost cardiomyocytes
Stimulation of endogenous cardiomyocytes
Neovascularisation

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Why is neovascularisation a good thing in CV disease?

Improved circulation to injured area

Paracrine effects improving CM replacement

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What are the challenges of transplanting cells to promote cardiac regeneration?

Immune rejection
Manufacture/ isolation of sufficient cells
Mode of delivery and clinical regulation

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What is the immune response in neonatal mouse hearts?

Embryonic macrophage infiltration
Revascularisation
Global cardimyocyte proliferation

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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