Stem Cells Technology, business, & ethics

1
Stem Cells Technology, business, ethics

• By Steve Mushero
• www.SteveMushero.com
• Swedish-American Chamber of Commerce
• Silicon Vikings

2
Overview

• A little about Stem Cells
• What are they good for ?
• Latest news, cool research
• Swedish contribution
• Ethics and the big issues
• How can we make money ?
• Future

3
What are stem cells ?

• Stem Root Source
• Stem cells are the source of all cells
• Some stem cells can become any cell type
• Eventually differentiate to 200 cell types
• Very complex, poorly understood process
• Several stages of differentiation
• Stem, blood, red blood, . . .
• Reversible ? Yes, no, maybe, perhaps, dont know

4
Where are the Stem Cells ?

• Two choices Embryo Adult
• Embryo
• Start with one single cell - the fertilized egg
  !!
• Most flexible - can become any cell type
• Two choices of embryo source
• Fertilized in the usual way (Man Woman)
• Cloned (use your own cells)
• Adult
• Present in normal tissues, including brain
• Have significant and poorly understood
  limitations

5
Getting Embryonic Stem Cells

• Need an embryo
• Old fashioned way - With egg sperm
• In Vitro Fertilization
• Most common
• Excess embryos (usually dozens created)
• Never implanted, so not aborted
• Fetal (Abortion) Used for some RD
• Therapeutic Cloning
• More exciting allows use of own cells
• Needed to eliminate rejection
• Not reproductive cloning
• Move in Congress to ban therapeutic cloning

6
Getting Embryonic Stem Cells

• Egg divides - first 2 cells, then 4, then 8 . . .
• Becomes Blastocyst
• Hollow ball with key cells inside
• Harvest at 3-5 days 30 cells in inner mass
• Embryo is destroyed in process, key ethical issue
• Two crucial embryonic cell characteristics
• Not yet differentiated (pluripotent)
• Can divide forever (key to culturing)

7
Adult Stem Cells

• Extracted in VERY small amounts from normal
  tissues
• Key to avoiding rejection issues your own cells
• Traditional rejection
• Graft vs. Host Disease The Stems Attack !
• Key to avoiding embryonic ethical issues
• Always partially differentiated (for now)
• BUT, research points to plasticity
• Liver stem cells to brain, muscle, and liver
• Bone marrow to muscle
• Brain stem cells to blood and muscle
• Not found in many key organs (Pancreas)
• Difficult to grow in culture cant mass produce
• Holy Grail - Is there a real master adult stem
  cell ?

8
Using Stem Cells

• Reverse damage
• Central Nervous System (CNS) damage
• Parkinsons Disease
• Multiple Sclerosis
• Heart Damage, Diabetes, Bone/Joint loss
• Cancer - Bone marrow transplant avoidance
• Fix genetic problems !!
• Severe Combined Immune Deficiency (SCID)
• Chronic Granulomatous Disease (CGD)
• Make good cells as needed !
• Make whole organs as needed !
• Kidney, Liver, Pancreas, maybe a Thumb

9
Recent Research

• Three ongoing key focal points
• Understand basic processes, especially
  differentiation
• Differentiation triggers
• Expand uses (usually embryonic cloning)
• Brain Lots of progress, especially in dopamine,
  neurons
• Blood Lots of immune system work
• Bones / Joints
• Pancreas (Diabetes)
• Liver Cells come from marrow ?
• Weekly announcements eyes, veins, heart muscle,
  skin
• Improve Adult Cells - Transdifferentiating /
  Plasticity
• Found a receptor/protein that limits plasticity
  (GCNF)
• Stanford found in Sept they cannot make other
  cells from adult blood stem cells
• How do adult cells work fusion, division
  Cancer risk ??

10
Treatment Progress

• Modest to date Very early in clinical process
• Parkinsons injections
• Mixed, but promising results
• Last week - Got neural stem cells to make
  dopamine
• Multiple Sclerosis
• Treat by killing own rogue stem cells
• Israel in June
• 22 month old infant with immune system failure
  (SCID)
• Cured via repaired bone marry stem cells
• Mouse research this year
• Extract and fix cell DNA
• Clone cells to get embryonic stem cells
• Inject new stem cells to fix immune system

11
Fixing an Immune System

• Baby with damaged immune system
• Remove bone marrow stem cells
• Fix genetic problem in DNA
• Culture cells to get useful volume
• Inject new immune cells into baby
• Normal immune system results !!
• Works when you have stem cells
• Mouse Immune Research - Cloned embryonic cells
• Remove ANY cell
• Fix DNA problem
• Clone cells to produce embryo/blastocyst
• Harvest stem cells
• Coax to differentiate into immune cells
• Inject new cells
• Crucial when body has no usable stem cells

12
Swedish Stem Cell Research

• Leading stem cell research center
• Over 30 teams, 300 people
• 38 of NIH approved cell lines (25 lines)
• Main centers - Karolinska, Sahigrenska, Lund
• Work in all areas embryonic, adult, cloning
• Legally favorable
• Therapeutic cloning allowed
• No embryonic issues
• Many research firsts
• Adult neural stem cell discovery
• First human embryonic stem cell cultures
• Number 1 or 2 per capita in patents, startups,
  biotechs, RD spending, researchers, funding

13
Swedish Companies

• Cell Therapeutics Therapies and broad stem cell
  applications
• Neuronova Adult neural stem cells for
  Parkinsons
• NsGene Neural stem cell therapies
• Vitrolife IVR and fertility system supplier

14
Ethics Whats Wrong ?

• Most issues surround Embryonic Stem Cells
• Embryo cannot survive cell extraction
• When does life begin ? What is an Embryo ?
• Does it matter if its cloned (no sperm) ?
• Does it matter if not implanted (not aborted) ?
• Is it okay if IVF embryos discarded anyway ?
• Abortions also a source and worry
• Will we harvest humans ?
• Already having kids for marrow matching
• But, must abort for stem cells (cord blood ?)

15
President Bush Chooses

• Balance scientific needs versus ethical
  religious issues
• Federally funded scientists may work only with
  existing lines
• Cannot create any new stem cell lines (kill no
  embryos)
• Bottom Line - 78 cell lines are now in registry
  (27 in USA)
• 14 approved sources in 6 countries - UCSF has 2
  lines
• 25 lines in Sweden, mostly in early stages (3
  ready)
• University of Gotenborg had 50 other Blastocysts,
  but rejected because embryo not yet destroyed
• 90 of mouse work over 20 years with only 5 lines
• Controversial
• Sufficient diversity
• Quality and purity issues
• Licensing, access issues
• Federal funding issue only
• Allows considerable private research and new
  lines
• Co-mingling decision Allows mixed use in same
  lab Big deal

16
Business / Future

• Significant funding for basic research
• Very International Sweden, US, India, Israel,
  Korea
• Massive promise in many of the most serious
  diseases
• Opportunities all along the development tree, in
  many specialties
• Suppliers, tools, equipment, reagents
• Stem cell sources (extraction from fat, etc.)
• Registries for matching (bone marrow)
• Processes for differentiating
• Actual therapies using cells (like drugs)
• Actual therapies targeting cells
• Entirely new views of the world

17
Future of Stem Cells

• Immense promise, though much work remains
• Therapies beginning to emerge SCID, Parkinsons
• Embryonic cells from cloning
• No actual embryo, reduced ethical issues
• Adult stem cells will work eventually
• Eliminate need for embryonic cells ethical
  issues
• Tremendous progress with applications
• Repaired genetic defects, maybe in womb
• New therapies for non-genetic diseases (Heart)
• New organs
• Repairing genetic defects will be common
• Change brown hair to blonde ? Ethics, ethics,
  ethics . . .

18
Thanks Questions

• Steve Mushero
• Steve_at_SteveMushero.com
• www.SteveMushero.com
• Swedish American Chamber of Commerce
• Silicon Vikings