1. The Why, What and How of Stem Cells - a primer
David Clapham
CiP Conference Oct 2016

2. Why are we interested?
Every cell in the body contains the same genetic material (DNA)
Theoretically could become any cell type
What differentiates a nerve cell from a skin cell?
Which parts of the genetic code are expressed
Different RNA and proteins
Influenced by epigenetics, micro environment (O2,pH, pressure, architecture), growth factors …………
Exact mechanism still not always fully understood
Stem cells much less specialised

3. Why do they exist?
To make the organism

4. To maintain and repair the organism
Typical adult human contains trillion cells
Cells are constantly dying (apoptosis) and being replaced
In addition
Trauma (e.g. cuts, bruises, muscle tears, broken bones)
Environmental insults
Pre cancerous events

5. What could Stem Cells be used for ?
For fundamental research
How do they form and differentiate
How do organs develop
What can go wrong and how can we stop it
etc ………….
For drug development
Finding drug hits
Toxicology testing (HEK cells)
Making biopharmaceuticals (reagents)
Some biopharms can only be made in mammalian cells
Direct therapy – repairing/replacing damaged tissue
Lab grown replacement tissues and organs

7. What has actually been done?
Bone marrow stem cell transplants for blood cancers now common place (also useful in angina symptom control)
Osteoarthritis trials very encouraging
Osteoporosis/bone healing ‘very effective’ in early trials
Stroke patients made a “remarkable recovery” in a trial that used donor stem cells injected into the brain
Attempts to treat Cystic Fibrosis mixed success (too rapid cell turn over/too many issues?) –gene therapy may be more effective
All successful direct therapy so far uses Adult Stem Cells (but HEK/embryonic cells used in research)

8. Cells with the ability to self replicate
Cells with the ability to self replicate. They are either undifferentiated or poorly differentiated and can thus differentiate into different kinds of cell

9. Several Types Unipotent produce only one cell type
Oligopotent can differentiate into only a few cell types
Multipotent can differentiate into a number of closely related cell types e.g. bone marrow cells
Pluripotent can differentiate into nearly all cells. Can be induced e.g. from skin cells
Totipotent (a.k.a. omnipotent) stem cells can differentiate into all cell types. Such cells can construct a complete, viable organism.  
In general the more potent the less abundant

10. How do they work?

11. Where can you find them? Embryos
up to the first 2 or 3 cell divisions - Totipotent
Amniotic fluid - potential source of pluripotent cells
Chord blood - Multipotent
Adult (mostly oligo or uni potent but can be multipotent with a few pluripotent)
Almost any tissue which can be harvested.
Bone marrow, Adipose tissue, blood, spleen, liver, skin etc

12. Can they be induced? In theory yes for all types
In practice - IPS cells from skin cells (and renal epithelial cells)

13. What are the technical issues?
Getting sufficient cells ?
some rich sources - but
numbers reduce with age
damage increases with age
collection not always straight forward
Cells can be cultured to mitigate
Sterility
Identity
Contamination
HEK cells are now decades old
Keeping them from differentiating
Getting them to differentiate ‘properly’
Immunological (rejection) issues?
not a problem if autologous
Some success with donor cells (potential risk of DNA contamination)
Dosing (right place, quantity and time)
Funding
Regulation

14. Possible Linked techniques
Each of these has potential for good but also troubling ethical questions
Sex cells derived from stem cells
Heritable changes
Cloning potential
So called ‘3 parent’ cells (mitochondrial correction)
Animal/human hybrids
Genetic manipulation