Stem Cells Regenerative Medicine Flashcards by Amal Seghir

What is a stem cells?

capable of self-renewal via cell division
can differentiate into many different cell types

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What are the 3 types of stem cells?

embryonic
adult
induced pluripotent stem cells

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What are some potential uses of stem cells?

blindness
myocardial infarction
wound healing
cancers
spinal chord injury

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What is the function of adult stem cells?

Supply new cells as a organism grows and replaces damaged cells
Are tissue specific and multipotent

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What are embryonic stem cells and what is they’re function?

supply all cells of developing embryo
pluripotent
pre implantation when the embryo is only a few days old

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What are induced pluripotent cells?

made in a lab
scientists take a biopsy and reprogram cells to produce pluripotent stem cells
used for drug development
used for cell replacement therapy (reduced chance of rejection by host)

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What do the different cells of the embryo differentiate into?

Endoderm - lung, pancrease
Mesoderm- heart muscle, red blood cells
Ectoderm - neuron, skin

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What are stem cell niches?

The special supportive micro environment for tissue-specific stem cells.

Interact with stem cells to regulate cell fate

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What do stem cell niches contain?

supporting ECM
neighbouring niche cells
secreted soluble signalling factors (eg. Growth factors and cytokines)
physical parameters (eg. Tissue stiffness, topography)
environmental signals (metabolites, hypoxia, inflammation)

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What are the limitations of embryonic stem cells?

Higher risk of tumour creation

Risk of being genetically different from the recipients cells - higher risk of rejection

Destroy human embryo - ethical

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What are the benefits of embryonic stem cells?

Pluripotent - may differentiate into any type of cell

Unlimited number of cells due to high cell potency

Very low probability of mutation induced damage in the DNA

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What are the limitation of adult stem cells?

Multipotent - unipotent - limited cell potency

Limited numbers may be obtained

Higher probability of mutation induced damage in the DNA - risk of disease

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What are the benefits of adult stem cells?

Compatible with recipients cells - low risk of rejection

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What are the limitations of induced pluripotent stem cells?

Higher probability of mutation induced damage in the DNA - risk of disease

Less growth potential then embryonic stem cells

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What are the benefits of induced pluripotent stem cells?

Low risk of rejection

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What 3 transcription factors are used in IPS?

Sox2

Oct3/4

Kif4

c-Myc (promotes DNA replication and relaxes chromatin structure)

What is the importance of transcription factors in IPS?

Activate target genes

Encode transcription factors which establish the pluripotent transcription factor network

Resulting in the activation of the epigenetic processes- establish pluripotent genome

How can in vivo imaging be used to track stem cell therapies?

Inserting a reporter gene into the stem cells

Aid the development and clinical translation of cell-based therapeutics by long term tracking in the preclinical and clinical settings

What happens during a heart attack?

Blood supply to the heart muscle is lost.

Cardiac muscle dies and is NOT replaced, as cardio myocyte turnover is low

Tethered are often fibrosis and scaring leading to decreased cardiac function and heart faliure

Research into therapies to replace lost cardiac cells and improve blood supply

ADULT HEART HAS LOW LEVEL ENDOGENOUS REGENERATIVE ABILITY

Give a example of a model of regenerate cardiac tissue.

Cardiac regeneration in adult zebra fish

How can the lymphatic system improve cardiac repair?

If the lymphatic system is stimulated with HFC

There’s a increased lymphatic response which removes tissue fluid from the inflammatory cells

Reduced lymphedema and inflammation

Further improves cardiac repair and function

Describe how cardiac lineages are made from IPSC.

IPCS are specified to pre cardiac mesoderm

By inhibition of GSK-3beta

Then the pre cardiac mesoderms are converted to cardiovascular progenitor cells

By inhibiting wet signalling

These progenitor cells can then differentiate into other cardiac cells using different transcription factors

What is Thymosin beta 4 (TB4) ?

Present in myocardial cells

Necessary for epicardial migration and coronary vasculature and cardiomyocyte survival.

What happens when Tb4 is inserted into adult hearts?

can stimulate epicardial outgrowth and neovascularisation

What happens when IPS cell sheet of heart muscle cells is added to a damaged human heart?

The study shows the cells did not seem to intigrate into the heart tissue But they may be releasing paracrine factors That help regenerate the damaged muscle

What happens when Epicardial FSTL1 expression is restored to the damaged heart muscle?

It promotes regeneration of pre-existing cardio myocytes in mouse and pigs. Could be a possible therapeutic avenue for post MI therapy

How can stem cell therapy help treat cancer?

Transplantation of stem cells reconstitutes healthy cells when undergoing chemo/radiotherapy Effector immune cells (T cells and NK) can be created from IPSC/ESCs Production of anti cancer vaccines MSCs/NSCs deliver genes, nano particles and oncolytic viruses Exosomes extracted from the culture of drug-priming MSCs/NSCs can target drugs to tumour sites

What are stem cell therapies for burns?

Replace lost skin cell types, speeding up endogenous healing Feta, fibroblasts: improve skin repair due to - high expansion ability, - low immunogenicity - intense secretion of bioactive substances Epidermal stem cells: - high proliferation rate - keep they’re potency and differentiation potential for long periods of time - generate most skin cell types Mesenchymal stem cells: - high differentiation potential - certain degree of plasticity - regulate tissue regeneration by producing growth factors, cytokines and chemokines IPSCs: - differentiate into fibroblasts, keratinocytes, and melanocytes

How can stem cell therapy be used for eye injury/disease?

Limbal stem cells are responsible for making new corneal cells too Replace damaged cells - if limbal cells are lost the cornea can no longer be repaired (affecting the ability of light to enter the eye, resulting in loss of vision) Limbal temp cells are collected from a healthy donor eye and are expanded in the laboratory to sufficient numbers and are TRANSPLANTED into the damaged eye of the patient. Repairs the cornea and permanently restores vision To avoid immune rejection the patient MUST HAVE A HEALTHY SECTION OF THE LIMBUS to collect the Limbal cells from - IPCS cells can be used, where fibroblast cells can be converted to limbal stem cells on exposure to the right signals

What is retinal pigment epithelium?

Single layer of post mitosis cells Acting as a selective barrier and regulator of the overlying photoreceptor Key role in retina maintenance- PARTS OF THE RETINA CAN DIE WITHOUT A FUNCTIONAL RPE (loss of vision)

How can stem cell therapy be used to treat age-related macular degeneration?

RPE cells have been made from both ESC and IPSc Several clinical trials

How can spinal injury be treated with stem cell therapy

Neural stem/progenitor cell (NSPC) integrate into sites of spinal chord injury Calcium imaging of NSPC in adult spinal chord injury showed NSPC grafts organise into localised and spontaneously active synaptic networks Stimulation using light caused a neuronal response in the graft and vice versa Behavioural stimulation also elicited focal synaptic responses within grafts Therefore neural progenitor grafts can resemble intact spinal chord ONGOING