Regenerative medicine

What is a stem cell?

an undifferentiated cell capable of self-renewal and producing differentiated cell types

What are the two fundamental properties of stem cells?

• Self-renewal — ability to produce more stem cells through cell division.

• Differentiation — ability to generate specialised cell types.

What is differentiation?

The process by which cells become specialised cell types

What does “self-renewal” mean?

The ability of a stem cell to divide while maintaining a population of stem cells.

Why are stem cells important for regenerative medicine?

they have the potential to replace, repair or regenerate damaged cells and tissues.

What is regenerative medicine?

A branch of research concerned with replacing, engineering or regenerating human cells, tissues or organs to restore or establish normal function

What are the “4 Rs” of regenerative medicine?

• Repair

• Replace

• Restore

• Regenerate

totipotent

can generate a whole organism, including embryonic cells e.g., the zygote

What does “pluripotent” mean?

can generate all cell types of the adult organism, but cannot generate extraembryonic tissue e.g., embryonic stem cells

What does “multipotent” mean?

A multipotent cell can generate multiple related cell types, generally within a particular lineage

Give examples of multipotent stem cells

• Neural stem cells

• Mesenchymal stem cells

• Blood/haematopoietic stem cells

What does “unipotent” mean?

Able to generate one cell type within a particular lineage

Where are embryonic stem cells derived from?

inner cell mass (ICM) of the blastocyst

What is the blastocyst?

An early embryonic developmental stage

What is one major advantage of ESCs?

High developmental potential

Why must ESCs be differentiated before transplantation?

Because transplantation of undifferentiated pluripotent cells carries a tumour risk

What are the major risks/issues associated with pluripotent stem cells?

• Tumour formation from undifferentiated cells

• Ethical issues associated with ESCs

• Genetic mutation/instability concerns, particularly with iPS cells.

What are the major advantages of adult stem cells?

• Present in many tissues

• No ethical issues associated with embryo use

• Potential for autologous/personalised use

• Lower tumour risk compared with pluripotent cells.

What happens to many adult stem cells under physiological conditions?

They may remain dormant/inactive and become activated by injury or regenerative signals

What are the major limitations of adult stem cells?

• Restricted developmental potential

• Generally multipotent rather than pluripotent

• Not immortal

• May require repeated administration.

What are iPSCs?

induced pluripotent stem cells are cells engineered/generated by scientists to behave like embryonic stem cells.

What is a major advantage of iPSCs

They can provide a potentially endogenous/personalised source of pluripotent cells without requiring embryonic stem-cell derivation

What are major concerns associated with iPSCs?

• Genetic instability/mutation risk

• Tumourigenicity

Where are haematopoietic stem cells (HSCs) found?

In the bone marrow

What is the main function of HSCs?

They generate all types of blood cells

Why are bone marrow transplants considered stem-cell therapy?

bone marrow transplantation involves transplantation of haematopoietic stem cells

Where can mesenchymal stem cells (MSCs) be found?

• bone marrow

• peripheral blood

• dental tissues

• adipose/fat tissue

What cell types can MSCs differentiate into

• Chondrocytes → cartilage

• Adipocytes → fat

• Osteocytes → bone

What is the current opinion on MSC transplantation

MSC transplantation may benefit many degenerative conditions, but engraftment and differentiation are negligible. Their effects are thought to involve bystander effects that help the patient's own tissues regenerate

What is the MSC/stem-cell secretome?

The collection of biologically active substances released by stem cells, including extracellular vesicles and soluble factors

What are the two major components of the stem-cell secretome

• Extracellular vesicles (EVs)

• Soluble proteins/factors

How can adult stem-cell secretome exert therapeutic effects?

• reduction of inflammation

• immunomodulation

• paracrine signalling

What can adipose-derived stem cells differentiate into

bone and cartilage cells

Why is adipose tissue an attractive source of stem cells

There is plenty of source material, and adipose-derived cells can mediate bystander effects

What are muscle stem cells also called?

Satellite cells

Where are muscle satellite cells located?

At the periphery of skeletal muscle fibres

What happens to muscle satellite cells following injury?

They become activated, proliferate and differentiate to help replace damaged muscle cells

What role do muscle satellite cells play during repeated exercise?

They contribute to muscle regeneration and muscle mass gain

Where are skin stem cells found?

In the epidermal layer of adult skin

where are neural stem cells

In the young human brain, particularly the hippocampus and lateral ventricles

What can neural stem cells generate?

Nerve cells and glial cells

What is the developmental potential of neural crest-derived stem cells (NCSCs)

NCSCs are more than multipotent, differentiating into mesodermal and ectodermal cells

What is the developmental potential of neural crest-derived stem cells

NCSCs are more than multipotent, differentiating into mesodermal and ectodermal cells

What is a neurosphere?

A sphere-like cluster of neural stem/progenitor cells formed under appropriate culture conditions

What are the three main symptoms of Parkinson's disease listed in the lecture?

• Slow movement

• Stiff/inflexible muscles

• Involuntary shaking/tremor

What happens in the 6-OHDA model of Parkinson's disease?

Injection of 6-OHDA into the midbrain causes loss of dopaminergic neurons

What was done with NCSCs in the Parkinson's disease model?

Undifferentiated NCSCs were transplanted into the striatum of the lesioned hemisphere approximately four weeks after the lesion

What was the outcome of NCSC transplantation in the 6-OHDA Parkinsonian rat model?

NCSCs reduced the symptoms in the model

Why could stem cells be useful for drug discovery?

They can provide human-derived cells for studying disease biology and potentially testing drugs in relevant cell types

Why might iPSCs be particularly valuable for personalised drug research?

they can potentially provide patient-specific pluripotent cells, allowing disease and drug responses to be studied using cells with the patient's genetic background.

What limitations should be considered when using stem cells in drug discovery?

• whether differentiated cells accurately reproduce mature human tissue

• genetic stability

• reproducibility