Spermatogonial stem cell transplantation into rhesus testes regenerates spermatogenesis producing functional sperm

Brian P. Hermann, Meena Sukhwani, Felicity Winkler, Julia N. Pascarella, Karen A. Peters, Yi Sheng, Hanna Valli, Mario Rodriguez, Mohamed Ezzelarab, Gina Dargo, Kim Peterson, Keith Masterson, Cathy Ramsey, Thea Ward, Maura Lienesch, Angie Volk, David K. Cooper, Angus W. Thomson, Joseph E. Kiss, Maria Cecilia T. PenedoGerald P. Schatten, Shoukhrat Mitalipov, Kyle E. Orwig

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    184 Scopus citations

    Abstract

    Spermatogonial stem cells (SSCs) maintain spermatogenesis throughout a man's life and may have application for treating some cases of male infertility, including those caused by chemotherapy before puberty. We performed autologous and allogeneic SSC transplantations into the testes of 18 adult and 5 prepubertal recipient macaques that were rendered infertile with alkylating chemotherapy. After autologous transplant, the donor genotype from lentivirus-marked SSCs was evident in the ejaculated sperm of 9/12 adult and 3/5 prepubertal recipients after they reached maturity. Allogeneic transplant led to donor-recipient chimerism in sperm from 2/6 adult recipients. Ejaculated sperm from one recipient transplanted with allogeneic donor SSCs were injected into 85 rhesus oocytes via intracytoplasmic sperm injection. Eighty-one oocytes were fertilized, producing embryos ranging from four-cell to blastocyst with donor paternal origin confirmed in 7/81 embryos. This demonstration of functional donor spermatogenesis following SSC transplantation in primates is an important milestone for informed clinical translation.

    Original languageEnglish (US)
    Pages (from-to)715-726
    Number of pages12
    JournalCell Stem Cell
    Volume11
    Issue number5
    DOIs
    StatePublished - Nov 2 2012

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    ASJC Scopus subject areas

    • Molecular Medicine
    • Genetics
    • Cell Biology

    Cite this

    Hermann, B. P., Sukhwani, M., Winkler, F., Pascarella, J. N., Peters, K. A., Sheng, Y., Valli, H., Rodriguez, M., Ezzelarab, M., Dargo, G., Peterson, K., Masterson, K., Ramsey, C., Ward, T., Lienesch, M., Volk, A., Cooper, D. K., Thomson, A. W., Kiss, J. E., ... Orwig, K. E. (2012). Spermatogonial stem cell transplantation into rhesus testes regenerates spermatogenesis producing functional sperm. Cell Stem Cell, 11(5), 715-726. https://doi.org/10.1016/j.stem.2012.07.017