Stem Cells Technology, business, & ethics
By Steve Mushero
www.SteveMushero.com
Swedish-American Chamber of Commerce & Silicon Vikings
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
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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, don’t know
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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
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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 R&D More exciting – allows use of own cells Needed to eliminate rejection Not reproductive cloning Move in Congress to ban therapeutic cloning
Therapeutic Cloning
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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 Not yet differentiated (pluripotent) Can divide forever (key to culturing)
Two crucial embryonic cell characteristics
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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; can’t mass produce Holy Grail - Is there a real master adult stem cell ?
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Using Stem Cells
Reverse damage
Central Nervous System (CNS) damage
Parkinson’s Disease Multiple Sclerosis
Heart Damage, Diabetes, Bone/Joint loss Cancer - Bone marrow transplant avoidance Severe Combined Immune Deficiency (SCID) Chronic Granulomatous Disease (CGD)
Fix genetic problems !!
Make good cells as needed ! Make whole organs as needed !
Kidney, Liver, Pancreas, maybe a Thumb
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Recent Research
Three ongoing key focal points Understand basic processes, especially differentiation
Differentiation triggers
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 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 ??
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Expand uses (usually embryonic & cloning)
Improve Adult Cells - Transdifferentiating / Plasticity
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Treatment Progress
Modest to date – Very early in clinical process Parkinson’s injections
Mixed, but promising results Last week - Got neural stem cells to make dopamine
Treat by killing own rogue stem cells 22 month old infant with immune system failure (SCID) Cured via repaired bone marry stem cells Extract and fix cell DNA Clone cells to get embryonic stem cells Inject new stem cells to fix immune system
Multiple Sclerosis
Israel in June
Mouse research this year
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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 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
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Mouse Immune Research - Cloned embryonic cells
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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 Therapeutic cloning allowed No embryonic issues Adult neural stem cell discovery First human embryonic stem cell cultures
Legally favorable
Many research firsts
Number 1 or 2 per capita in patents, startups, biotechs, R&D spending, researchers, funding
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Swedish Companies
Cell Therapeutics – Therapies and broad stem cell applications Neuronova – Adult neural stem cells for Parkinson’s NsGene – Neural stem cell therapies Vitrolife – IVR and fertility system supplier
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Ethics – What’s Wrong ?
Most issues surround Embryonic Stem Cells
Embryo cannot survive cell extraction Does it matter if it’s cloned (no sperm) ? Does it matter if not implanted (not aborted) ?
When does life begin ? What is an Embryo ?
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 ?)
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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)
14 approved sources in 6 countries - UCSF has 2 lines 25 lines in Sweden, mostly in early stages (3+ ready)
Bottom Line - 78 cell lines are now in registry (27 in USA)
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 Allows considerable private research and new lines Co-mingling decision – Allows mixed use in same lab – Big deal
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Federal funding issue only
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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
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Future of Stem Cells
Immense promise, though much work remains Therapies beginning to emerge – SCID, Parkinson’s Embryonic cells from cloning
No actual embryo, reduced ethical issues Eliminate need for embryonic cells & ethical issues Repaired genetic defects, maybe in womb New therapies for non-genetic diseases (Heart) New organs Change brown hair to blonde ? Ethics, ethics, ethics . . .
Adult stem cells will work eventually
Tremendous progress with applications
Repairing genetic defects will be common
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Thanks & Questions
Steve Mushero
Steve@SteveMushero.com
www.SteveMushero.com
Swedish – American Chamber of Commerce & Silicon Vikings
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