Stem Cell Reviews

, Volume 1, Issue 4, pp 337–343 | Cite as

Nonviable human pre-implantation embryos as a source of stem cells for research and potential therapy

Article

Abstract

Human embryonic stem cells are derived from the inner cell mass of the human blastocyst. Presumably normal (frozen/thawed) human preimplantation embryos that remain unused following assisted reproduction procedures have provided the main source of blastocysts for stem cell derivation. Alternatively, embryos have been generated from gametes donated for the unique purpose of in vitro fertilization, blastocyst culture, and stem cell isolation. This article describes two previously published methods—and the background to those methods—that allow the use of nonviable embryos excluded from transfer and cryopreservation as a source of stem cells. The first method is based on the observation that some blastomeres from embryos with abnormal division during the first 3–5 d in culture can continue very limited development in isolation. When aggregated in a chimaeric form, some of these blastomeres can contribute to the formation of normally organized blastocysts. Blastocysts so obtained provide a route to embryonic stem cells from otherwise nonviable embryos. Thus the inner cell masses of blastocysts obtained from trisomic embryos were placed on feeder cells and cultured for seven additional days, following which the resulting cell colonies were examined for chromosome content. The second method concerns embryos diagnosed with specific chromosome abnormalities many of which are incompatible with life. Some of these aneuploidies do not preclude development to the blastocyst stage in culture. A proportion of these cells were found to be disomic and the cultures were shown to express OCT-4, a molecular marker for pluripotent cells. This apparent correction of the trisomic state in some cells within the colonies suggests that embryos with cromosomal abnormalities incompatible with life may be another source of human embryonic stem cells.

Index Entries

Human embryonic stem cells chimeric blastocysts aneuploidy trisomy nonviable abnormal development 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Marquez C, Sandalinas M, Bahce M, Alikani M, Munné S. Reprod Biomed Online 2000;1:17–26.PubMedCrossRefGoogle Scholar
  2. 2.
    Magli MC, Gianaroli L, Ferrareti AP. Endocrinol 22, 2001;183(Suppl. 1):S29-S34.Google Scholar
  3. 3.
    Tarkowski AK. Nature 1959;184:1286–1287.PubMedCrossRefGoogle Scholar
  4. 4.
    Moore NW, Adams CE, Rowson LE. J Reprod Fertil 1968;17:527–531.PubMedCrossRefGoogle Scholar
  5. 5.
    Rossant J. J Embryol Exp Morph 1976;36:283–290.PubMedGoogle Scholar
  6. 6.
    Willadsen SM. Nature 1979;277:298–300.PubMedCrossRefGoogle Scholar
  7. 7.
    Willadsen SM. J Embryol Exp Morph 1981;65:165–172.PubMedGoogle Scholar
  8. 8.
    Geber S, Winston RM, Handyside AH. Hum Reprod 1995;10:1492–1496.PubMedGoogle Scholar
  9. 9.
    Staessen C, Van Steirteghem A. Hum Reprod 1998;13:1625–1631.PubMedCrossRefGoogle Scholar
  10. 10.
    Alikani M and Willadsen SM. Reprod Biomed Online 2002;5:56–58.PubMedCrossRefGoogle Scholar
  11. 11.
    Tarkowski AK. Int J D Biol 1998;42:903–908.Google Scholar
  12. 12.
    Alikani M, Cohen J, Tomkin G, Garrisi GJ, Mack C, Scott R. Fertil Steril 1999;71:836–842.PubMedCrossRefGoogle Scholar
  13. 13.
    Alikani M, Schimmel T, Willadsen SM. Mol Hum Reprod 2005;11:335–344.PubMedCrossRefGoogle Scholar
  14. 14.
    Alikani M, Calderon G, Tomkin G, Garrisi J, Kokot M, Cohen J. Hum Reprod 2000;15:2634–2643.PubMedCrossRefGoogle Scholar
  15. 15.
    Johnson MH, McConnell J, Van Blerkom J. J Embryol Exp Morph 1984;83(Suppl):197–231.PubMedGoogle Scholar
  16. 16.
    Kidder GM, Rains J, McKeon J. Proc Nat Acad Sci USA 1987;84:3718–3722.PubMedCrossRefGoogle Scholar
  17. 17.
    Petzoldt U and Muggleton-Harris A. Development 1987;99:481–491.PubMedGoogle Scholar
  18. 18.
    Willadsen SM and Polge C. Vet Rec 1981;108:211–213.PubMedGoogle Scholar
  19. 19.
    Tarkowski AK, Ozdzenski W, Czolowska R. Int J Dev Biol 2001;45:591–596.PubMedGoogle Scholar
  20. 20.
    Veiga A, Calderon G, Barri PN, Coroleu B. Hum Reprod 1987;2:321–323.PubMedGoogle Scholar
  21. 21.
    Alikani et al., unpublishedGoogle Scholar
  22. 22.
    Racowsky C, Combelles CM, Nureddin A, et al. Reprod Biomed Online 2003;6:323–331.PubMedCrossRefGoogle Scholar
  23. 23.
    Stone BA, Greene J, Vargyas JM, Ringler GE, Marrs RP. Am J Obstet Gyn 2003;192:2014–2019.CrossRefGoogle Scholar
  24. 24.
    Jackson KV, Ginsberg ES, Hornstein MD, Rein MS, Clarke RN. Fertil Steril 1998;70:60–66.PubMedCrossRefGoogle Scholar
  25. 25.
    Van Royen E, Mangelschots K, Vercruyssen M, De Neubourg D, Valkenburg M, Ryckaert G, Gerris J. Hum Reprod 2003;18:1062–1069.PubMedCrossRefGoogle Scholar
  26. 26.
    Thomson JA, Solter D. Dev Biol. 1989;31:580–583.CrossRefGoogle Scholar
  27. 27.
    Everett CA and West JD. Zygote 1996;4:59–66.PubMedCrossRefGoogle Scholar
  28. 28.
    Boediono A, Suzuki T, Li LY, Godke RA. Mol Reprod Devel 1999;53:159–170.PubMedCrossRefGoogle Scholar
  29. 29.
    Edwards RG and Pool T. Reprod Biomed Online 2002;5:103.PubMedCrossRefGoogle Scholar
  30. 30.
    Everett CA and West JD. Genet Res 1998;72:225–228.PubMedCrossRefGoogle Scholar
  31. 31.
    Fehilly CB, Willadsen SM, Tucker EM. J Reprod Fertil 1984;70:347–351.PubMedCrossRefGoogle Scholar
  32. 32.
    Tang PC, Ritchie WA, Wilmut I, West JD. Zygote 2000;8:33–43.PubMedCrossRefGoogle Scholar
  33. 33.
    Munné S. Placenta 2003;24 Suppl B:S70-S76.PubMedCrossRefGoogle Scholar
  34. 34.
    Munné S, Chen S, Fischer J, et al. Fertil Steril 2005;84:331–335.PubMedCrossRefGoogle Scholar
  35. 35.
    Sandalinas M, Sadowy S, Alikani M, Calderon G, Cohen J, Munné S. Hum Reprod 2001;16:1954–1958.PubMedCrossRefGoogle Scholar
  36. 36.
    Magli MC, Jones GM, Gras L, Gianaroli L, Korman I, Trounson AO. Hum Reprod 2000;15:1781–1786.PubMedCrossRefGoogle Scholar
  37. 37.
    Munné S, Velilla E, Colls P, et al. Fertil Steril 2005;84:1328–1334.PubMedCrossRefGoogle Scholar
  38. 38.
    Kalousek DK, Langlois S, Barrett I, et al. Am J Hum Genet 1993;52:8–16.PubMedGoogle Scholar
  39. 39.
    Ledbetter DH and Engel E. Hum Mol Genet 1995;4:1757–1764.PubMedGoogle Scholar
  40. 40.
    Wolstenholme J. Prenat Diagn 1996;16:511–524.PubMedCrossRefGoogle Scholar
  41. 41.
    Kalousek DK, Howard-Peebles PN, Olson SB, et al. Prenat Diagn 1991;11:743–750.PubMedCrossRefGoogle Scholar
  42. 42.
    Tarin JJ, Conaghan J, Winston RM, Handyside AH. Fertil Steril 1992;58:970–976.PubMedGoogle Scholar
  43. 43.
    Los FJ, van Opstal D, van den Berg C, et al. Prenat Diagn 1998;18:659–668.PubMedCrossRefGoogle Scholar
  44. 44.
    Munné S, Magli C, Bahçe M, et al. Prenat Diagn 1998;18:1459–1466.PubMedCrossRefGoogle Scholar

Copyright information

© Humana Press Inc 2005

Authors and Affiliations

  1. 1.Tyho-Galileo Research LaboratoriesWest Orange
  2. 2.Reprogenetics, LLCWest Orange

Personalised recommendations