Nonhuman primate parthenogenetic stem cells

Kent E. Vrana, Jason D. Hipp, Ashley M. Goss, Brian A. McCool, David R. Riddle, Stephen J. Walker, Peter J. Wettstein, Lorenz P. Studer, Viviane Tabar, Kerrianne Cunniff, Karen Chapman, Lucy Vilner, Michael D. West, Kathleen A. Grant, Jose B. Cibelli

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    162 Scopus citations

    Abstract

    Parthenogenesis is the biological phenomenon by which embryonic development is initiated without male contribution. Whereas parthenogenesis is a common mode of reproduction in lower organisms, the mammalian parthenote fails to produce a successful pregnancy. We herein describe in vitro parthenogenetic development of monkey (Macaca fascicularis) eggs to the blastocyst stage, and their use to create a pluripotent line of stem cells. These monkey stem cells (Cyno-1 cells) are positive for telomerase activity and are immunoreactive for alkaline phosphatase, octamer-binding transcription factor 4 (Oct-4), stage-specific embryonic antigen 4 (SSEA-4), tumor rejection antigen 1-60 (TRA 1-60), and tumor rejection antigen 1-81 (TRA 1-81) (traditional markers of human embryonic stem cells). They have a normal chromosome karyotype (40 + 2) and can be maintained in vitro in an undifferentiated state for extended periods of time. Cyno-1 cells can be differentiated in vitro into dopaminergic and serotonergic neurons, contractile cardiomyocyte-like cells, smooth muscle, ciliated epithelia, and adipocytes. When Cyno-1 cells were injected into severe combined immunodeficient mice, teratomas with derivatives from all three embryonic germ layers were obtained. When grown on fibronectin/laminin-coated plates and in neural progenitor medium, Cyno-1 cells assume a neural precursor phenotype (immunoreactive for nestin). However, these cells remain proliferative and express no functional ion channels. When transferred to differentiation conditions, the nestin-positive precursors assume neuronal and epithelial morphologies. Over time, these cells acquire electrophysiological characteristics of functional neurons (appearance of tetrodotoxin-sensitive, voltage-dependent sodium channels). These results suggest that stem cells derived from the parthenogenetically activated nonhuman primate egg provide a potential source for autologous cell therapy in the female and bypass the need for creating a competent embryo.

    Original languageEnglish (US)
    Pages (from-to)11911-11916
    Number of pages6
    JournalProceedings of the National Academy of Sciences of the United States of America
    Volume100
    Issue numberSUPPL. 1
    DOIs
    StatePublished - Sep 30 2003

    ASJC Scopus subject areas

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    Vrana, K. E., Hipp, J. D., Goss, A. M., McCool, B. A., Riddle, D. R., Walker, S. J., Wettstein, P. J., Studer, L. P., Tabar, V., Cunniff, K., Chapman, K., Vilner, L., West, M. D., Grant, K. A., & Cibelli, J. B. (2003). Nonhuman primate parthenogenetic stem cells. Proceedings of the National Academy of Sciences of the United States of America, 100(SUPPL. 1), 11911-11916. https://doi.org/10.1073/pnas.2034195100