1. What do we need to know to become stem cell literate?

2. AND THE VALUE OF HUMAN LIFE
The challenge of stem cell research…..
MAINTAIN A COMMITMENT TO BOTH THE ADVANCEMENT OF SCIENCE FOR THE BETTERMENT OF MANKIND AND TO THE DEFENSE OF HUMAN FREEDOM, DIGNITY
AND THE VALUE OF HUMAN LIFE

3. Two Characteristics of Stem Cells
Able to make more them of themselves (self-renewal) through cell division.
Under experimental conditions can become committed to a specific organ or tissue (differentiation).

4. FUNCTIONAL DEFINITION OF A STEM CELL
Cell Divided
Differentiation
Stem Cell: A cell that can both renew itself and produce new cells that will form a tissue.

5. What type of stem cells exist?
1 – Multipotent stem cell: give rise to a SMALL NUMBER of cell types found in a mature tissue that can only yield specialized cell types (dental stem cell)
2 - Pluripotent stem cell: give rise to ANY cell types found in the body (embryonic or induced pluripotent stem cell)

6. MULTIPOTENT
“ADULT” (post-birth)
STEM CELLS
CAN MAKE MULTIPLE
CELL TYPES, BUT
NOT ALL CELL TYPES
IN PEOPLE LIKE US

7. Human pluripotent stem cells hold Great promise for medical therapy…
PLURIPOTENT- Can develop (differentiate) into ALL cell types and specialized tissues in the body
EXPANDABLE - Ability to be grown for a long time in laboratory culture without losing “self-renewal” capacity
SELF RENEWAL – can produce cells that become all cell types AND a cell that remains PLURIPOTENT

8. Where do
embryonic
stem cells
come from?

9. EMBRYONIC STEM CELLS AND “POTENCY”

10. An “ethical threshold” is driving stem cell science
PROBLEM: Human embryonic stem cells
can not presently be obtained without destroying
human embryos.
CHALLENGE: Is there a way for scientists to
“harvest” pluripotent stem cells without creating,
destroying of harming human embryos.
Are there other ways to make sources of such
stem cells?

11. Finding ethically-uncontroversial ways to advance human embryonic stem cell research
Somatic cell nuclear transfer (SCNT) provides donor-specific stem cells (Hello Dolly!!)
THIS IS HUMAN CLONING…… 11

12. SOMATIC CELL NUCLEAR TRANSFER OR CLONING
CAN WE FIND NEW
SOURCES OF EMBRYONIC
STEM CELLS –
SOMATIC CELL
NUCLEAR TRANSFER
OR CLONING
Remove nucleus from
adult donor cell and inject
into an egg
Nucleus undergoes reprogramming
to behave like pluripotent stem cell

13. Somatic Cell Nuclear Transfer
Problems with
Somatic Cell Nuclear Transfer
Ethical obligations to manipulating and sourcing donor eggs (donor abuse)
Very expensive
Inefficient – problems with embryo survival
Cloning of an identical human being.

14. What is the risk of human cloning??
Asexual reproduction to produce an organism identical to a previously existing, human
THERAPEUTIC CLONING -
human cloning to derive cells for therapy
REPRODUCTIVE CLONING –
human cloning for purpose of reproducing
another human

15. NOBEL PRIZE FOR CREATING PLURIPOTENT STEM CELLS….
UNCONTROVERSIAL PLURIPOTENT STEM CELLS?

16. HOW REPROGRAMMING MAY CHANGE THE WORLD
Alzheimer
Parkinson
Diabetes
ALS
SMA …
Rodolfa and Eggan 16

17. Questions
Are hESCs still necessary? Can we decide if iPSC can and should replace hESC?
Would using iPSC resolve all ethical dilemmas about pluripotent stem cell research?
Are these ethically-relevant differences between iPSC vs. hESC?

18. Safety And Effectiveness Of Future Therapies
Safety And Effectiveness Of Future Therapies? Safety Standards For Cells
Science Issue: Both iPSC and hESC are defined by making tumors in animals.
Ethical Problem: First clinical iPSC trial halted for safety reasons.
Solution: no clear conclusions on safety or value of iPSC vs hESC for human therapy.

19. Mitochondrial Disease
The mitochondria are cells in the cytoplasm— sometimes hundreds. Each cell has 37 genes compared to 20-30,000 in the cell’s nucleus.

21. Gene Therapy Gene Therapy
Somatic Cell Germ Line
Gene Therapy Gene Therapy
MORAL BOUNDARY

22. Options for prospective mother with mt disease
Obtain donor egg with partner’s sperm
Have prenatal genetic diagnosis on intending mother’s eggs to determine the eggs with least mt mutations.
adopt a child
Go through ooplasmic transfer; MST, or PNT

23. CRISPR/Cas9 System
Clustered regularly interspaced short palindromic repeats (CRISPRs) and CRISPR-associated (Cas) proteins

24. Genome Editing Technologies (CRISPR) And Human Germline Genetic Modification
Possible to insert, delete, or modify DNA with greatly increased specificity and efficiency.
Use to correct genetic defects or introduce other potentially therapeutic changes.
The potential for modification of the human germline.
Concern that genome editing technologies might be used to modify embryos before there are data sufficient to support use.

25. What is it?
derived from a natural process found in bacteria to protect themselves from pathogens
targets genes for editing and regulating
Can modify genes in embryos that can cross the “germ line”
Horizon Licenses Harvard University Gene-Editing Technology. (2013). Drug Discovery & Development.

27. To initiate gene modification,
sgRNA
(single guide RNA)
Cas9 complex
Cas9 nuclease

28. Protospacer Adjacent Motif (PAM)
Target Sequence
Gene of Interest

29. Needed Basic Scientific Research or CRISPR- Much To Be Learned
Research to understand and improve the technique of genome editing itself.
How to best use genome editing as a tool to address fundamental research questions.
Research to generate preliminary data for the development of human somatic (non-germline) applications.
Research to inform the plausibility of developing safe human reproductive applications.

30. What Should We Do With CRISPR?
Basic research?
Clinical application?
Public engagement?
Governance?
Clinical reproductive purposes?