Skip to main content

Parthenogenetic Embryonic Stem Cells in Nonhuman Primates

  • Chapter
  • First Online:
Trends in Stem Cell Biology and Technology

Abstract

Parthenogenesis is a naturally occurring process where an oocyte is activated without sperm contribution. In mammals, parthenogenetic (PG) embryos cannot develop to term. The most commonly used method of artificially making diploid PG embryos is using via chemical activation of the egg and by preventing extrusion of the second polar body. Parthenogenetic embryonic stem (PGES) cells are derived from the inner cell mass of PG embryo at the blastocyst stage. They are pluripotent, i.e., they can differentiate into all three germ layers: ecto-, meso-, and endoderm, and can be propagated as stem cells in culture for prolonged periods of time. PGES cells offer an easily obtainable pool of stem cells that can be used as a source for derivation of autologous tissues, albeit limited to females in reproductive age. PGES cells derivation does not require destruction of a viable embryo and therefore bypasses the ethical debates surrounding the use of naturally fertilized embryos. Nonhuman primates are the closest species to human in the tree of evolution and therefore are excellent models for studying human development and diseases. PGES cells from nonhuman primate and human parthenogenetically activated oocyte have recently been derived (13). These cells offer a valuable tool for studying the developmental, differentiation, and functional potential of the PGES cells in the context of their clinical application in organ and tissue transplantations in humans.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 89.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Matsuda T, Wake N. Genetics and molecular markers in gestational trophoblastic disease with special reference to their clinical application. Best Pract Res Clin Obstet Gynaecol 2003;17:827–36.

    Article  PubMed  Google Scholar 

  2. Mutter GL. Role of imprinting in abnormal human development. Mutat Res 1997;396:141–7.

    Article  PubMed  CAS  Google Scholar 

  3. Surti U, Hoffner L, Chakravarti A, Ferrell RE. Genetics and biology of human ovarian teratomas. I. Cytogenetic analysis and mechanism of origin. Am J Hum Genet 1990;47:635–43.

    PubMed  CAS  Google Scholar 

  4. Mai Q, Yu Y, Li T, et al. Derivation of human embryonic stem cell lines from parthenogenetic blastocysts. Cell Res 2007;17:1008–19.

    Article  PubMed  CAS  Google Scholar 

  5. Revazova ES, Turovts NA, Kochetkova OD, et al HLA homozygous stem cell lines derived from human parthenogenetic blastocysts. Cloning Stem Cells 2008 10:11–24.

    Article  PubMed  CAS  Google Scholar 

  6. Revazova ES, Turovts NA, Kochetkova OD, et al. Patient-specific stem cell lines derived from human parthenogenetic blastocysts. Cloning Stem Cells 2007;9:432–49.

    Article  PubMed  CAS  Google Scholar 

  7. Strain L, Warner JP, Johnston T, Bonthron DT. A human parthenogenetic chimaera. Nat Genet 1995;11:164–9.

    Article  PubMed  CAS  Google Scholar 

  8. Surani MA. Parthenogenesis in man. Nat Genet 1995;11:111–3.

    Article  PubMed  CAS  Google Scholar 

  9. Mitalipov SM, Nusser KD, Wolf DP. Parthenogenetic activation of rhesus monkey oocytes and reconstructed embryos. Biol Reprod 2001;65:253–9.

    Article  PubMed  CAS  Google Scholar 

  10. Sotomaru Y, Katsusava Y, Hatada I, Obata Y, Sasaki H, Kono T. Unregulated expression of the imprinted genes H19 and Igf2r in mouse uniparental fetuses. J Biol Chem 2002;277:12474–8.

    Article  PubMed  CAS  Google Scholar 

  11. Ogawa H, Wu Q, Komiyama J, et al Disruption of parental-specific expression of imprinted genes in uniparental fetuses. FEBS Lett 2006;580;5377–84.

    Article  PubMed  CAS  Google Scholar 

  12. Lyle R. Gametic imprinting in development and disease. J Endocrinol 1997;155:1–12.

    Article  PubMed  CAS  Google Scholar 

  13. Zvetkova I, Apedaile A, Ramsahoye B, et al. Global hypomethylation of the genome in XX embryonic stem cells. Nat Genet 2005;37:1274–9.

    Article  PubMed  CAS  Google Scholar 

  14. Wobus AM, Boheler KR. Embryonic stem cells: prospects for developmental biology and cell therapy. Physiol Rev 2005;85:635–78.

    Article  PubMed  CAS  Google Scholar 

  15. Cibelli JB, Grant KA, Pahapman KB, et al. Parthenogenetic stem cells in nonhuman primates. Science 2002;295:819.

    Article  PubMed  CAS  Google Scholar 

  16. Vrana KE, Hipp JD, Goss AM, et al. Nonhuman primate parthenogenetic stem cells. Proc Natl Acad Sci U S A 2003;100 Suppl 1:11911–6.

    Article  Google Scholar 

  17. Sanchez-Pernaute, R, Stder L, Ferrari D, et al Long-term survival of dopamine neurons derived from parthenogenetic primate embryonic stem cells (Cyno-1) after transplantation. Stem Cells 2005;23:914–22.

    Article  PubMed  Google Scholar 

  18. Ferrari D, Sanchez-Pernaute R, Lee H, Studer L, Isacson O. Transplanted dopamine neurons derived from primate ES cells preferentially innervate DARPP-32 striatal progenitors within the graft. Eur J Neurosci 2006;24:1885–96.

    Article  PubMed  Google Scholar 

  19. Dighe V, Clepper L, Pedersen D, et al. Heterozygous embryonic stem cell lines derived from nonhuman primate parthenotes. Stem Cells 2008;26:756–66.

    Article  PubMed  CAS  Google Scholar 

  20. Cheng L. More new lines of human parthenogenetic embryonic stem cells. Cell Res 2008;18:215–7.

    Article  PubMed  CAS  Google Scholar 

  21. Sapienza C. Parental imprinting of genes. Sci Am 1990;263:52–60.

    Article  PubMed  CAS  Google Scholar 

  22. Tang Wy, Ho SM. Epigenetic reprogramming and imprinting in origins of disease. Rev Endocr Metab Disord 2007;8:173–82.

    Article  PubMed  Google Scholar 

  23. Swales AK, Spears N. Genomic imprinting and reproduction. Reproduction 2005;130:389–99.

    Article  PubMed  CAS  Google Scholar 

  24. Fujimoto A, Mitalipov SM, Kuo HC, Wolf DP. Aberrant genomic imprinting in rhesus monkey embryonic stem cells. Stem Cells 2006;24:595–603.

    Article  PubMed  CAS  Google Scholar 

  25. Newman-Smith ED, Werb Z. Stem cell defects in parthenogenetic peri-implantation embryos. Development 1995;121:2069–77.

    PubMed  CAS  Google Scholar 

  26. Horii T, Kimura M, Morita S, Nagao Y, Hatada I. Loss of genomic imprinting in mouse parthenogenetic embryonic stem cells. Stem Cells 2008;26:79–88.

    Article  PubMed  CAS  Google Scholar 

  27. Kono T, Obata Y, Wu Q, et al. Birth of parthenogenetic mice that can develop to adulthood. Nature 2004;428:860–4.

    Article  PubMed  CAS  Google Scholar 

  28. Kono T, Sotomaru Y, Katsuzawa Y, Dandolo L. Mouse parthenogenetic embryos with monoallelic H19 expression can develop to day 17.5 of gestation. Dev Biol 2002;243;294–300.

    Article  PubMed  CAS  Google Scholar 

  29. Mitalipov S, Clepper L, Sritanaudomchai H, Fujimoto A, Wolf D. Methylation status of imprinting centers for H19/IGF2 and SNURF/SNRPN in primate embryonic stem cells. Stem Cells 2007;25:581–8.

    Article  PubMed  CAS  Google Scholar 

  30. Runte M, Kroisel PM, Gillessen-Kaesbach G, et al. SNURF-SNRPN and UBE3A transcript levels in patients with Angelman syndrome. Hum Genet 2004;114:553–61.

    Article  PubMed  CAS  Google Scholar 

  31. Reik W, Maher ER. Imprinting in clusters: lessons from Beckwith–Wiedemann syndrome. Trends Genet 1997;13:330–4.

    Article  PubMed  CAS  Google Scholar 

  32. Nicholls RD, Saitoh S, Horsthemke B. Imprinting in Prader–Willi and Angelman syndromes. Trends Genet 1998;14:194–200.

    Article  PubMed  CAS  Google Scholar 

  33. Hurst LD, McVean GT. Growth effects of uniparental distomes and the conflict theory of genomic imprinting. Trends Genet 1997;13:436–43.

    Article  PubMed  CAS  Google Scholar 

  34. Sotomaru Y, Kawase Y, Ueda T, et al Disruption of imprinted expression of U2afbp-rs/U2af1-rs1 gene in mouse parthenogenetic fetuses. J Biol Chem 2001;276:26694–8.

    Article  PubMed  CAS  Google Scholar 

  35. Poirier F, Chan CT, Timmons PM, Robertson EJ, Evans MJ, Rigby PW. The murine H19 gene is activated during embryonic stem cell differentiation in vitro and at the time of implantation in the developing embryo. Development 1991;113:1105–14.

    PubMed  CAS  Google Scholar 

  36. Han VKM, Carter AM. Spatial and temporal patterns of expression of messenger RNA for insulin-like growth factors and their binding proteins in the placenta of man and laboratory animals. Placenta 2000;21:289–305.

    Article  PubMed  CAS  Google Scholar 

  37. Pringle KG, Roberts CT. New light on early post-implantation pregnancy in the mouse: roles for insulin-like growth factor-II (IGF-II)? Placenta 2007;28:286–97.

    Article  PubMed  CAS  Google Scholar 

  38. Minniti CP, Luan D, O’Grady C, Rosenfeld RG, Oh Y, Helman LJ. Insulin-like growth factor II overexpression in myoblasts induces phenotypic changes typical of the malignant phenotype. Cell Growth Differ 1995;6:263–9.

    PubMed  CAS  Google Scholar 

  39. Pacher M, Seewald MJ, Mikula M, et al. Impact of constitutive IGF1/IGF2 stimulation on the transcriptional program of human breast cancer cells. Carcinogenesis 2007;28:49–59.

    Article  PubMed  CAS  Google Scholar 

  40. Prelle K, Wobus AM, Krebs O, et al. Overexpression of insulin-like growth factor-II in mouse embryonic stem cells promotes myogenic differentiation. Biochem Biophys Res Commun 2000;277:631–8.

    Article  PubMed  CAS  Google Scholar 

  41. Weber MM, Fottner C, Schmidt P, et al. Postnatal overexpression of insulin-like growth factor II in transgenic mice is associated with adrenocortical hyperplasia and enhanced steroidogenesis. Endocrinology 1999;140:1537–43.

    Article  PubMed  CAS  Google Scholar 

  42. Moorehead RA, Sanchez OH, Baldwin RM, Khokha R. Transgenic overexpression of IGF-II induces spontaneous lung tumors: a model for human lung adenocarcinoma. Oncogene 2003;22:853–7.

    Article  PubMed  CAS  Google Scholar 

  43. Petrik J, Pell JM, Arany E, et al. Overexpression of insulin-like growth factor-II in transgenic mice is associated with pancreatic islet cell hyperplasia. Endocrinology 1999;140:2353–63.

    Article  PubMed  CAS  Google Scholar 

  44. Newman-Smith E, Werb Z. Functional analysis of trophoblast giant cells in parthenogenetic mouse embryos. Dev Genet 1997;20:1–10.

    Article  PubMed  CAS  Google Scholar 

  45. Kawahara M, Wu Q, Takahashi N, et al. High-frequency generation of viable mice from engineered bi-maternal embryos. Nat Biotechnol 2007;25:1045–50.

    Article  PubMed  CAS  Google Scholar 

  46. Kono T, Kawahara M, Wu Q, et al. Paternal dual barrier by Ifg2-H19 and Dlk1-Gtl2 to parthenogenesis in mice. Ernst Schering Res Found Workshop 2006;23–33.

    Google Scholar 

  47. Sheehy E, Conrad SL, Brigham LE, Hiura H, Obata Y. Estimating the number of potential organ donors in the United States. N Engl J Med 2003;349;667–74.

    Article  PubMed  Google Scholar 

  48. Coombes JM, Trotter JF. Development of the allocation system for deceased donor liver transplantation. Clin Med Res 2005;3:87–92.

    Article  PubMed  Google Scholar 

  49. Nagy A, Gocza E, Diaz EM, et al. Embryonic stem cells alone are able to support fetal development in the mouse. Development 1990;110:815–21.

    PubMed  CAS  Google Scholar 

  50. Nagy A, Rossant J, Nagy R, Abramow-Newerly W, Roder JC. Derivation of completely cell culture-derived mice from early-passage embryonic stem cells. Proc Natl Acad Sci U S A 1993;90:8424–8.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Jose Bernardo Cibelli .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2009 Humana Press, a part of Springer Science+Business Media, LLC

About this chapter

Cite this chapter

Ragina, N., Cibelli, J. (2009). Parthenogenetic Embryonic Stem Cells in Nonhuman Primates. In: Baharvand, H. (eds) Trends in Stem Cell Biology and Technology. Humana Press. https://doi.org/10.1007/978-1-60327-905-5_3

Download citation

Publish with us

Policies and ethics