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Stem Cell Update: Telling Hype from Hope

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Title: Stem Cell Update: Telling Hype from Hope


1
Stem Cell Update Telling Hype from Hope
Ricki Lewis November 2008
2
What are stem cells?
Self-renew and can differentiate.
3
(No Transcript)
4
3 basic stem cell typesES iPS adult
5
3 steps identifyisolate/extract/alteranalyze/d
eliver
6
1. The gold standard human embryonic stem (hES)
cells
7
Why hES cells?
  • To study pathogenesis
  • Drug development
  • Therapeutics (cell therapy, tissue engineering)
  • To compare iPS cells to -- how similar are they?

8
NOT to clone humans
9
hES cells from fertility clinic leftovers
10
Other embryo sources
  • From fertility clinics
  • failed to fertilize
  • early embryonic arrest
  • no cleavage
  • spindle defects
  • aneuploid

11
SCNT paved the way to iPS cells.
12
2. Induced pluripotent stem (iPS) cells
  • Select somatic cell
  • Deliver Yamanaka factor genes
  • OCT4, SOX2, KLF4, c-MYC
  • Add cocktails, get desired cell types
  • Use!
  • Study development
  • Test drugs
  • Treat patient

New buzzword reprogram Old term
dedifferentiate
13
Yamanaka factors Oct4 Klf4 Sox2 c-Myc
iPS cells
14
iPS cells from 2 ALS patients astrocytes
(red) motor neurons (green)
15
Harvard iPS Core
  • ADA deficiency/SCID
  • Shwachman-Bodian-Diamond syndrome
  • Gaucher disease III
  • Duchenne MD
  • Becker MD
  • Parkinson Disease
  • Huntington Disease
  • Type 1 diabetes
  • Trisomy 21
  • Lesch-Nyhan carriers

16
Do iPS cells hES cells?
  • Cell surfaces
  • Telomerase
  • Gene expression
  • Yield cells from all 3 germ layers
  • Normal chromosomes
  • DNA profile of donor

17
1rst proof of concept sickle cell disease(NEJM
2/28/08 -- iPS cells in mice)
18
Potential challenges with iPS cells
  • Low rate of reprogramming
  • Many combos possible
  • Genetic modification to alter them ( gene
    therapy)
  • Teratoma
  • Viral insertional mutation
  • Cancer
  • Transcriptome epigenetics differ for iPS and ES
  • Somatic mutation

19
Tailored iPS cells are just the beginning
Recapitulating organogenesis
20
3. Adult Stem CellsOne source medical waste
  • Horse hooves
  • Cat dog testicles
  • Liposuction leftovers
  • Blood
  • Roadkill
  • Zoo deaths
  • Skin after weight loss
  • Fluid from knee
  • Biopsies
  • Extra blood vessels
  • Extra brain tissue

21
Extra-embryonic structures
  • Membranes
  • Human amniotic epithelial cells have ES cell
    markers.
  • Become stem-like in culture
  • Medical waste

22
Umbilical cord stem cells
  • Not cord blood cells
  • Like mix of ES bone marrow cells
  • High division rate
  • Self-renewal
  • No spontaneous differentiation
  • Medical waste

23
SHED best acronym
Stem Cells from Human Exfoliated Deciduous Teeth
Bone, cartilage, fat, mesenchyme BioEden Tooth
Cell Bank 585 89/year
24
In praise of fat (Vet-Stem)
25
3 applications basic research (development
disease)drug discovery/developmenttreatments
(implants, transplants, signals)
26
1. Basic research progeria
  • Progerin expressed in adult mesenchymal stem
    cells reveals development rerouted to favor bone
    over fat

27
2. Drugs
  • See origins in ES neural progenitors
  • Identified glutamate pathway as mechanism of
    birth defects

28
  • Treatments
  • Promising Pilot Studies Using Adult Stem Cells
  • Batten disease
  • Parkinsons disease
  • ALS (many
  • Epidermolysis bullosa hematopoietic)
  • Toothlessness
  • Chronic critical limb ischemia
  • Muscular dystrophies
  • Oral sub-mucosal fibrosis
  • clinicaltrials.gov

29
  • Requirements for stem cell-based treatments
  • Ethical source (opinion)
  • Cells must divide in vitro
  • Cryopreservation without damage
  • Pluripotent
  • Dont cause cancer
  • Self-renewal
  • Not immunogenic

30
Bronchopulmonary dysplasia
  • Cord pericytes
  • Self-renew
  • Become alveolar type II pneumocytes, which make
    surfactant yield type I, which exchange gases
    but dont divide

31
Eyes a great source of stem cells
32
Corneal transplants fail if no limbal cells
  • In 10 years, we will have eliminated the need
    for cell therapies. If we find the signals to
    regenerate the cornea, we can deliver them in
    drops.
  • Sajjad Aahmad
  • Northeast England Stem Cell Institute

33
RPE (Sally Temple)
  • From vitrectomy cadavers (no mice)
  • Normally RPE yields 6 types of retinal cells
  • ES medium yields all 3 germ layers.
  • Divide in culture up to 11 times.
  • In clinical trials to treat Parkinsons disease.

34
Cardiac not ready for prime time
  • Stem cells must differentiate as smooth muscle,
    endothelium, cardiac muscle
  • Must synchronize
  • Lack adult K channels
  • Ejection fraction improvement too little
  • Could be natural recovery/healing

decellularization???
35
Neural stem cells
  • 1912 discovered in rodent brains, dismissed as
    artifact

36
Neural Stem Cells
  • 1960s -- newborn guinea pigs have stem cells near
    brain ventricles.
  • Hypothesis if these mammals, born able to walk,
    need neural stem cells, so do human infants.

37
1980s birds learning songs gain brain cells,
near ventricles. Have counterparts in mammalian
brain.
38
Neural stem cells
  • 1990s neural stem cells found in tree shrews,
    marmosets, rhesus monkeys

39
Brain marrow
  • 1996-1998 BrdU in brains of cancer patients
  • 2001 Neural stem cells in cadavers
  • 2006 Neural progenitors from epilepsy surgery

40
Human neural stem cell resource
  • Stem cells from different brain parts, different
    diseases
  • From cadavers surgeries
  • Available to researchers

http//www.nhnscr.org/ Childrens Hospital of
Orange County
41
Hype !
42
Proliferation of companies
43
Banking cells
  • Umbilical cord
  • Bone marrow mesenchymal stem cells
  • Future???

44
Hair skin replacement
  • Male pattern baldness
  • Facial rejuvenation
  • Leg ulcers
  • Hair follicle stem cells to smooth muscle to
    vascular grafts

45
Neostem very small embryonic-like stem cells
(note typo)
46
Neostem spokesperson Suzanne Somers
  • my own stem cells will be banked as
    bio-insurance. Now I am prepared for my future as
    the beneficiary of medical benefits while I am
    alive.

7500 to extract 750/year to store
47
menstrual stem cell service
48
Cellerant Therapeutics
  • CLT-008 will keep people
  • alive after a nuclear attack.

49
(No Transcript)
50
For athletes, the next fountain of youth?
  • NYT, 3/29/07
  • MDs speculating
  • No info, no news
  • Banking stem cells for future injuries
  • Not performance enhancement because self

51
Selling hope
  • Companies (most not in U.S) sell treatments that
    use
  • Cord blood stem cells
  • A patients own cells
  • Fetal cells

52
Stem cell company red flags
  • No clinical trials
  • Testimonials
  • No follow-up
  • Not done in U.S.
  • PubMed no-show
  • Too many claims
  • Evasive or repetitive language
  • Errors in basic biology

Medical Tourism
53
In memory of Glenn Nichols
1950-2008
54
False promises ALS
  • Patients treated with the companys NurOwnTM
    therapeutic cells are expected to enjoy a rapid
    recovery and much enhanced quality of life.

55
False promises
  • The company is initiating a series of efficacy
    and safety studies toward a cure for ALS.
  • (SOD mice on rotarod)

56
A case of mistaken identity
  • ALS embryonic stem cells from cell
    suspensions obtained from growth zones of
    cadaverous embryos systems and organs.

Cells from 4-8 week embryos are not hES cells.
57
A look into the not-too-distant future
Signals instead of cells
For study guide www.stemcellsymphony.com
58
  • Stem cell activity
  • Choose disease or injury
  • Identify affected molecules, cells, tissues,
    organs
  • Identify genes proteins
  • Deliver!
  • Troubleshooting
  • How to not cause cancer
  • How to target effects
  • How to prevent adverse effects
  • How to monitor response
  • 6. Write an ad for your product or treatment.
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