Guidelines for Human Embryonic Stem Cell Research (2005) / Chapter Skim
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2 Scientific Background of Human Embryonic Stem Cell Research
2 Scientific Background of Human Embryonic Stem Cell Research
Pages 29-46
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From page 29... ...
, the cells of the inner cell mass differentiate to form the embryonic tissue layers of the developing fetus. Embryonic stem cells are usually derived from the primitive (undifferentiated)
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From page 30... ...
At the blastocyst stage, cells of the inner cell mass are undifferentiat ed and pluripotent; that is, they have the potential to differentiate into all cells of the fetus except the placenta. If separated from the blastocyst and cultured, the cells of the inner cell mass can be converted into embryonic stem cells that are also pluripotent and can be propa gated extensively while maintaining that potential.
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From page 31... ...
Developmentally relevant signaling factors can also be used to induce mES cells to differentiate into specific cell types in vitro, including hematopoietic stem cells, beating cardiac muscle cells, neuronal progenitors, endothelial cells, and bone cells. In some cases, those differentiated cell types can be transplanted into animals to form functional tissues (Lanza et al., 2004)
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From page 32... ...
. Those examples of interspecies differences indicate that if one is to identify signals that cause stem cells to differentiate into specialized cells, work needs to continue with both hES and mES cells.
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From page 33... ...
NUCLEAR TRANSFER TO GENERATE STEM CELLS Most work on hES cells has taken place with a relatively small number of cell lines obtained from excess blastocysts donated from in vitro fertilization (IVF) programs.
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From page 34... ...
As in organ or bone marrow transplantation, one solution is to develop large banks of genetically diverse hES cells to increase the chances that matches can be found for all patients who need them. That is one strong medical reason for generating additional hES cell lines from a wider spectrum of the popu lation.
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From page 35... ...
NT blastocysts, like normal blastocysts, can be used to derive embryonic stem cells from their inner cell masses. The picture shown is of a normal human blastocyst (http://www.fosep.org/images/blastocyst2.gif)
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From page 36... ...
This proof of the principles behind generating NT hES cells has made plausible the derivation of more such lines from specifically defined genetic backgrounds. It is important to note that stem cells made using NT result from an asexual process that does not involve the generation of a novel combination of genes from two "parents." In this sense, it may be more acceptable to some than the creation of blastocysts for research purposes by IVF (NIH HERP, 1994)
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From page 37... ...
SOURCES OF OOCYTES FOR NT ES CELLS At current rates of success of generation of NT blastocysts and ES cells, one major limitation of expansion of this approach will be the availability of oocytes for NT. Current and possible future sources of such oocytes include excess oocytes and unfertilized oocytes from IVF procedures, oocytes matured from ovariectomies or fetal ovaries from pregnancy terminations, oocyte donation, derivation of oocytes from nonreproductive material, and use of nonhuman oocytes.
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From page 38... ...
• Use of nonhuman oocytes. Obtaining large numbers of oocytes from nonhu man mammals is relatively easy, and the use of such oocytes to derive NT blastocysts and stem cells has been considered.
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From page 39... ...
But it needs consideration when pluripotent hES cells or their neural derivatives, such as neural stem cells, are used. It seems highly unlikely that hES cells could contribute to the germline after implantation into a postnatal animal because the germline is set aside very early in fetal development.
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From page 40... ...
Similar experiments have been invaluable in testing the capacity of neuronal progenitors derived in vitro from mES cells by transplantation into chicken embryos (Wichterle et al., 2002) ; it seems clear that there will be a need or desire to conduct similar experiments to test the potential of hES cells and their derivatives.
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From page 41... ...
A clear example of how such research must proceed is offered by a study in which mES cells were coaxed to develop in vitro into precursors of motor neurons (restricted potential neuronal progenitors or neuronal stem cells) , which were then transplanted into chicken embryos, where they differentiated into motor neurons (Wichterle et al, 2002)
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From page 42... ...
These are the types of essential experiments for which the guidelines proposed later in this report are designed to provide a framework for ethical and responsible conduct. • Additional hES cell lines must be generated because experience from studies of mES cells shows that lines differ in their potential and do not always retain their potential on extended culture.
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From page 43... ...
• Research is needed to understand how to maintain the self-renewing capac ity of hES cells over long-term culture and expansion. In the mouse, the LIF JAK-STAT pathway of signaling molecules is necessary and sufficient for self-renewal, but it is not sufficient to maintain hES cells in the stem cell state (Daheron et al., 2004)
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From page 44... ...
• All the foregoing procedures will necessitate means of testing the potential of the derived cells to contribute usefully when implanted and for adverse side effects; such tests will undoubtedly be required by FDA before any therapeu tic use. That requirement will necessitate development of protocols for effec tive and ethical testing of the potential of hES cells and their derivatives (or adult stem cells)
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From page 45... ...
If hES cells can be directed to differentiate into specific cell types, they may be more likely to mimic the in vivo response of cells and tissues to the drug being tested and so offer safer models for drug screening. Similarly, hES cells could be used to screen potential toxins.
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