Stem cells and regenerative medicine Flashcards
What are stem cells?
- Capable of self-renewal via cell division
- Can differentiate into many different cell types
- Provide new cells as organism grows and can replace cells that are damaged or lost
- Targeted by researchers for their therapeutic potential
What are the potential uses of stem cells?
- Blindness
- Wound healing
- Myocardial infarction
- Cancers
What are the different types of stem cells?
- induced pluripotent cells
- made in the lab from skin or fat biopsy
- reprogramme them exposing them to factors to produce pluripotent stem cells
- used in cell therapy and is specific to the patient
- embyronic stem cells
- pluripotent, dervied from embryos in the blastocyst stage before implantation
- go through many rounds of cell division before differentiation
- can give rise to ectoderm, endoderm and mesoderm
- adult stem cells - very rare and tissue specific and multipotent
How does a totipotent embryonic stem cells differentiate?
What are stem cell niches?
= Tissue-specific stem cells are maintained in special supportive microenvironments
- Niches interact with stem cells to determine cell fate
- Protect the cells from depletion
- They secrete soluble signalling factors
What are the postivies and negatives of embyronic stem cells?
Positives:
- unlimited growth to differntiate into any kind of cell
- unlimited numbers of cell due to high cell potency
- very low probability of mutation-induced damage in the DNA
Negatives:
- higher risk of tumour creation
- risk of being genetically different from the recipicent’s cells - higher risk of rejection
What are the postivies and negatives of adult stem cells?
Positives:
- compatible with recipient’s cells - low risk of rejection
- less risk of tumour creation
Negative:
- limited cell potency
- limited numbers may be obtained
- risk of diseases from high probability of mutation
What are the postivies and negatives of induced pluripotent stem cells?
Positive:
- compatible with recipent’s cells - low risk of rejection
Negatives:
- limited numbers may be obtained
How can you generate iPSC cells?
How does stem cell tracking work?
Done by inserting a reporter gene like fluorescence
When they are transplanted back into animals in trials, non-invasive in vivo long-term cell tracking can be used to study how the stem cells behave
What is neovascularisation?
= improved circulation to injured area and paracrine effects improving cardiomyocytes and coronary heart disease
Can be achieved via:
- Cell-based therapies
- Cell-free therapies
How does cardiac regeneration differ between large and small mammals?
In zebrafish and mouse, following a heart injury there is complete regeneration
- We see re-expression of gene developmental programmes early after the injury in the epicardium = reactivation
- Followed by cardiomyocyte differentiation - formation of a clot then degrading as cardiomyocytes proliferate and regenerate
In larger animals like humans and pigs, clot does not resolve and instead remodels to form a scar which affects cardiac function
- If we can rein act the effects in zebrafish and mouse, we may be able to use this therapeutically in these larger mammals
How can we improve cardiac repair and function?
In a normal or controlled injury response, the lymphatic system does not clear excess fluid leading to oedema and inflammation –> leads to poor cardiac repair and function
If the lymphatic system is modified with a form of VEGFC, there is an increased lymphatic response which improves the clearance of tissue fluid in inflammatory cells, reduces oedema and inflammation, and further improves cardiac repair and function
How do cardiac cells arise from iPSCs?
- iPSCs are specified towards pre-cardiac mesoderm by inhibition of glycogen synthase kinase (GSK-3B)
- Pre-cardiac mesoderm is the downstream switch for signalling pathways including Wnt Signalling
- Further inhibition of Wnt signalling then leads to the differentiation of cardiac progenitor cells
- Different signalling molecules then differentiates these cells towards specialised cardiac energies:
How does stem cell therapy in the treatment of cancer?
- Chemotherapy kills cancerous cells and transplantation of stem cells reconstitutes healthy cells
- Production of anti-cancer vaccines
- MSCs/NSCs deliver genes, nanoparticles and oncolytic viruses to tumour niche due to intrinsic tumour tropism
