From Iusmgenetics

[edit] Stem Cells

• Stem cells have two features: self renewal and differentiation.

• Early experiments in which we though HSCs could dediff into other tissue types were actually misinterpretations of HSC fusion with endogenous cells of other types.

• We are sill trying to use HSCs to fix non-heme disease states though, and there is some reality.
• One major limitation to using HSCs is the inability to expand the population ex-vivo.

• Sources of ESCs include "left-overs" from fertility treatment and SCNT.

• The blastocyst is the center of ethical discussions on embryonic stem cell use; how much moral status does a blastocyst have?

• SCNT: remove donor oocyte nucleus, place another nucleus in the oocyte, trick oocyte into feeling fertilized; develops into embryo.
• Therapeutic cloning is SCNT with pt's own donated nucleus into an oocyte (unlikely to be from the donor).
• Reproductive cloning is the same as therapeutic but you implant it in an organism.
  • Not allowed in humans anywhere!
  • Not allowed in any animals in some states.

• Reasons reproductive cloning isn't allowed in humans:
  • Most implants die soon after implantation.
  • Many offspring have developmental abnormalities.
  • Human cloning could then be performed simply for organ harvest.
• Therapeutic and reproductive cloning are regulated only at the state level.
  • Most states have no law at all.
  • Indiana does not allow therapeutic cloning or reproductive cloning (in any animal).

• Bush (2001) allowed use of 60 existing embryonic cell lines.
• Obama (2009) allowed production of new embryonic cell lines:
  • from well informed, freely consenting fertility-therapy donors
  • with private funds

• iPSCs can self renew and can differentiate.
• iPSCs don't require a blastocyst stage and therefore avoid many ethical concerns.
• One study has shown that Sickle Cell Disease could be fixed in a mouse by gene-correcting autologous iPSCs and reimplanting.

• iPSCs are awesome because:
  • immunologically match their pt
  • can be repaired
  • can be repeatedly differentiated into many different types of tissue
  • avoid blastocyst stage and therefore ethical issues
• iPSCs aren't perfect because:
  • produced via C-myc which is an oncogene and therefore have a risk of oncogenesis
  • produced via retroviral insertion of transcription factors and therefore have a risk of insertional mutagenesis
  • still need lots of work to figure out how to purposefully differentiate them into specific tissue types

• We are starting to figure out how to induce iPSCs without c-myc.
• We are starting to figure out how to induce iPSCs only as pluripotent as needed:
  • to get to the HSC stage, only, instead of going all the way "back" to the fully potent iPSC.
  • means lower risk in teratomas in the pt.