8 - Stem cells

Key features of stem cells

Unspecialised

Self-renewal

Can differentiate into specialised forms

Non-direct differentiation of stem cells to specialised cells

Stem cells give rise to progenitor cells that have limited capacity to self-renew before differentiating

Totipotent

Capable of forming every cell in the embryo and placenta

Pluripotent

Can form every cell in embryo but not in the placenta

Multipotent

Forma range of different cell types

Unipotent

Generate one type of specialised cell

Somatic stem cells

Present in adult and foetal tissue

Restricted potential and not immortal

What day in development are embryonic stem cells no longer present

Day 7

On day 7, what have the ESCs become

Differentiated into epiblast and hypoblast

Applications of stem cells

Scientific discovery

Drug development

Gene therapy

Production of specific cell types for therapeutic transplantation

How are stem cells used in scientific discovery

Understand disease mechanisms

How cells and tissues form in development

Synthetic mouse embryo

Investigate molecular mechanisms that regulate human embryogenesis

Somewhat overcomes the limitations of using human ESCs

Stem cells in drug development

Rapid screening

Rule out drugs sooner on in the process

Useful for generating cell types that cannot be easily obtained from primary source

Personalised medicine

Patient in novel stem cell therapy for EB

Young boy with mutation in gene encoding laminin beta3

Treatment for EB using stem cells

Skin biopsy

Cells infected with retrovirus with healthy copy of LAMB3

Grew into sheets

What stem cells are used in bone marrow transplant and leukaemia

Haematopoietic

Technical barriers in stem cell treatment

Risk of tumour formation

Difficulty in stem cell behaviour regulation

Tracking cells following admission

Immune rejection

Solution to risk of tumour formation in stem cell treatment

Strategy to remove all pluripotent stem cells before transplantation

Solution to direction of stem cell behaviour

Better understanding of the basic mechanisms that control stem cell fate so growth conditions can be created

What is required to track stem cells after administration

Imaging technologies

Solutions to immune rejection of stem cells

Immunosuppressants

Generate pluripotent stem cells that are genetically identical to the patients

Ethical issues of human reproductive cloning

Unsafe

Unethical

Unwarranted

Illegal

Why is reproductive cloning unsafe

Many animals die before birth

Medical problems

Why is reproductive cloning unethical

Possibility of severe medical conditions

Human cloning = human experimentation

No justifiable reason to do it

Reasons for human reproductive cloning

Male infertility

Lesbian couples can have children

Raelians

Group that believes they are the cloned descendants of extra-terrestrial

4 factors for the reprogramming of human fibroblasts to generate iPS cells

Oct4

Sox2

c-Myc

Klf4

Retrovirus

RNA virus which inserts a DNA copy of its genome into the host in order to replicate

What body sites are immune to ESC therapies

Brain and spine

Oligodendrocytes

Key support cells in the CNS that produce myelin

ESC therapy for spinal cord injury

Based on studies in rats

hESC-derived oligodendrocytes

Injected into spinal cord injury lesion

ESC based therapy for Parkinson’s disease

Replacement of dopamine with precursor L-3-4-dihydroxyphenylanine (L-DOPA)

Limited in long term

Cause of Parkinson’s disease

Death of dopamine-producing neurons in the substantia nigra deep in the brain

Possible explanation for differences in success of foetal stem cell therapy

Ways the cells were handled prior to transplantation

Lack of immunosuppressant cover

Difficulties with use of foetal stem cell therapy

Many foetuses needed to treat each person

Age is critical

Ethics

Potential side effects

What are MSCs

Mesenchymal stromal cells

Consequences of stem cell hype

Unrealistic expectations