slide1 n.
Download
Skip this Video
Loading SlideShow in 5 Seconds..
Stem cells and neuroscience: Biology, applications, and controversy PowerPoint Presentation
Download Presentation
Stem cells and neuroscience: Biology, applications, and controversy

Loading in 2 Seconds...

play fullscreen
1 / 19

Stem cells and neuroscience: Biology, applications, and controversy - PowerPoint PPT Presentation


  • 94 Views
  • Uploaded on

Stem cells and neuroscience: Biology, applications, and controversy. Noam Y. Harel, MD, PhD 12 November 2013 Brain and Behavior. Disclosures. I do not have any financial or other conflicts of interest to disclose for this learning session.

loader
I am the owner, or an agent authorized to act on behalf of the owner, of the copyrighted work described.
capcha
Download Presentation

PowerPoint Slideshow about 'Stem cells and neuroscience: Biology, applications, and controversy' - tryna


An Image/Link below is provided (as is) to download presentation

Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author.While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server.


- - - - - - - - - - - - - - - - - - - - - - - - - - E N D - - - - - - - - - - - - - - - - - - - - - - - - - -
Presentation Transcript
slide1

Stem cells and neuroscience: Biology, applications, and controversy

Noam Y. Harel, MD, PhD

12 November 2013

Brain and Behavior

disclosures
Disclosures
  • I do not have any financial or other conflicts of interest to disclose for this learning session.
  • I do not affirm that all discussions of drug use will be consistent with either FDA or compendia-approved indications. Off-label and experimental drugs may be discussed.
learning objectives
Learning Objectives
  • Understand the origin and potential tissue types created by different classes of stem cells.
  • Understand the potential benefits and risks of stem cell applications.
  • Become versed in discussing the questions that will frequently be raised by patients regarding stem cells.
slide4
Improve cleanup – macrophages instead of oligos?

Reduce inflamm & scarring – steroids; chondroitinases; etc

Add guidance scaffold – Schwanns; olfactory ensheathing glia; etc

Replace growth factors – but can CNS neurons respond? gradients?

Trigger RAGs – cAMP modulators (rolipram); direct ‘gene therapy’

Rescue growth cones– calcium; microtubule stabilizers (eg taxol)

Block extrinsic inhibitors – Mabs; receptor decoys; RhoA inhibitors

Excite circuits– transmitter agonists; K+blockers; electrical stim; etc

Replace neurons – Stem cells

Remyelinate axons – Stem cells

Rehabilitate!!

Strategery: Repair and Recovery

Targets anyone?

  • – ESSENTIAL IN CONJUNCTION WITH ALL THE ABOVE
slide5

Stem Cells: Natural Sources

  • Embryonic
    • Derived from inner cell mass of blastocyst (4-5d post fertilization)
      • Usually from excess IVF-derived embryos
      • NOT from aborted fetuses (much later stage)
      • Results in non-viable embryo*
  • Source for PLURIpotent stem cells
    • can form tissue from endo/meso/ectoderm
    • not trophoblast
    • immortal/renewable
slide6

Stem Cells: Natural Sources

  • Fetal
    • Derived from fetal or extra-fetal tissue
      • eg amniotic, umbilical cord blood, placental tissue
      • does not need to disrupt fetal viability
    • Few PLURIpotent cells, mostly MULTIpotent cells
    • Immortal/renewable
slide7

Stem Cells: Natural Sources

  • Adult
    • Stem cells found within many mature tissues
      • Obvious: bone marrow, skin, GI
      • Not as obvious: adipose; cardiac; brain; dental pulp
      • synonyms: mesenchymal stem cell; multipotent stromal cell
    • MULTIpotent to OLIGOpotent
      • eg hematopoietic SCs  all hematopoietic cell types
      • eg neural SCs  glial and neural cells
      • transdifferentiation possible, eg cardiac  neuro, etc
    • Renewable
    • Autologous banking
slide8

Stem Cells: Synthetic

  • Somatic cell nuclear transfer
    • adult somatic cell nuclei + enucleated donor egg cells
    • Adult nucleus reprogrammed by donor egg cytoplasm
    • PLURIpotent
    • Patient-derived nuclear genes, but egg-derived mitochondrial genes
    • Used to clone animals; theoretically could be used to clone humans

John Gurdon

slide9

Stem Cells: Synthetic

  • Induced pluripotent stem cells (iPS)
    • Adult somatic cells + activated “stem cell genes”
    • PLURIpotent
    • 100% autologous

Shinya Yamanaka

slide10

Stem Cells: Synthetic

  • In vivo induced totipotent (iPS)
    • Transgenic mouse + activated “stem cell genes” leads to multiple teratomas
    • TOTIpotent SCs
slide11

Stem cell uses

  • Developmental studies
    • How are different cell types formed?
  • Patient-specific cells for in vitro drug screening
  • Cell transplants
    • To replace degenerated/lost tissue (neurons, cardiac, etc)
    • To support local tissue with growth factors, etc
    • Remember, usually need to PRE-differentiate the SCs first!
  • ORGAN transplants!
    • Three dimensional SC cultures now generating liver buds, mini-brains in vitro
slide12

Stem cells: Best targets?

  • Neurodegenerative diseases
    • HD – one type of neuron, one site
    • ALS, PD – one type of neuron, but many sites
    • Alzheimer’s – Too diffuse
  • Stroke
    • Replace cells (many types) in affected area
  • TBI; SCI
    • More axonal than neuronal injury
    • But likely to benefit from growth factors, remyelination
  • All of above will require adjunctive rehab to properly guide graft integration and plasticity
slide13

Scientific & technical issues

  • What needs to be replaced? Neurons? Glia? Axons?
  • Optimal degree & type of pre-differentiation pre-transplant?
  • Risks – neoplasm; rejection; procedural complications
slide14

Ethical issues

  • “Old days” (when embryos were the only source for pluripotent stem cells):
    • When does life begin? Are we destroying life?
  • Then and now:
    • Human (and animal) cloning?
    • Where does life begin? Are we creating life?
    • Is paying women for egg donations and/or pregnancy coercive?
    • Is not paying the sources of successful cell lines unfair?
    • Should stem cell treatments be sold as a commodity to desperate patients before the risks and safeguards are better worked out?
slide15

Stem Cells: caveat emptor

  • Stem cells! Get your stem cells right here!
slide16

Stem Cells: caveat emptor

  • Stem cells! Get your stem cells right here!
    • ZERO approved indications for pluripotent stem cells
      • Hematopoietic stem cells are in use (BMT)
    • “Clinics” charge exorbitant fees – for what?
      • Unclear composition of cellular injections
      • Tumorigenic?
      • Infections?
      • No systematic pre/post-care treatment plan
      • No systematic follow-up for efficacy or safety
      • No control treatment
slide17

Stem Cells: caveat emptor

  • Stem cells! Get your stem cells right here!
    • ZERO approved indications for pluripotent stem cells
      • Hematopoietic stem cells are in use (BMT)
    • “Clinics” charge exorbitant fees – for what?
      • Unclear composition of cellular injections
      • Tumorigenic?
      • Infections?
      • No systematic pre/post-care treatment plan
      • No systematic follow-up for efficacy or safety
      • No control treatment
    • Difficult to dissuade individual patients/families
      • More good will be done by enrolling in rigorous trials
        • Great need for more innovative trial designs
learning objectives1
Learning Objectives
  • Understand the origin and potential tissue types created by different classes of stem cells.
  • Understand the potential benefits and risks of stem cell applications.
  • Become versed in discussing the questions that will frequently be raised by patients regarding stem cells.
slide19
ABAD, M. ET AL. (2013) Reprogramming in vivo produces teratomas and iPS cells with totipotency features. Nature 502:340-345.

LANCASTER, M. ET AL. (2013) Cerebral organoids model human brain development and microcephaly. Nature 501:373-379.

LINDVALL, O. & KOKAIA, Z. (2010) Stem cells in human neurodegenerative disorders--time for clinical translation? J ClinInvest 120:29-40.

OKITA, K. & YAMANAKA, S. (2011) Induced pluripotent stem cells: opportunities and challenges. Philos Trans R SocLond B BiolSci 366:2198-2207.

PAPPA, K. & ANAGNOU, N. (2009) Novel sources of fetal stem cells: where do they fit on

the developmental continuum? RegenMed 4:423-433.

TAKEBE, T. ET AL. (2013) Vascularized and functional human liver from an iPSC-derived organ bud transplant. Nature 499:481-484.

Further Reading