@article{7769cf33e22d4d4d996ea31d549078b1,
title = "Spermatogonial stem cell transplantation into rhesus testes regenerates spermatogenesis producing functional sperm",
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.",
author = "Hermann, {Brian P.} and Meena Sukhwani and Felicity Winkler and Pascarella, {Julia N.} and Peters, {Karen A.} and Yi Sheng and Hanna Valli and Mario Rodriguez and Mohamed Ezzelarab and Gina Dargo and Kim Peterson and Keith Masterson and Cathy Ramsey and Thea Ward and Maura Lienesch and Angie Volk and Cooper, {David K.} and Thomson, {Angus W.} and Kiss, {Joseph E.} and Penedo, {Maria Cecilia T.} and Schatten, {Gerald P.} and Shoukhrat Mitalipov and Orwig, {Kyle E.}",
note = "Funding Information: We would like to acknowledge the outstanding work of Tony Battelli, Pam Wintruba, and Joe Hrach, the lab animal staff at Magee-Womens Research institute, who were critical to the conduct of these experiments. Artwork for the graphical abstract was produced by Dr. Bart Phillips. We are grateful to Drs. Robert Donahue and Cynthia Dunbar of the National Heart, Lung and Blood Institute, NIH, who provided critical advice for PBSC transplantation in nonhuman primates. Drs. Tony Plant and Judy Cameron provided advice about central line catheter placement in nonhuman primates. We also thank Drs. Regina Norris, Danielle Sweeney, David Rodeberg, and Francis Schneck from the Departments of Urology and General Surgery at the Children{\textquoteright}s Hospital of Pittsburgh of UPMC for their assistance with subcapsular testis biopsies. The FUGW lentiviral backbone was provided by Dr. Carlos Lois, University of Massachusetts. The anti-CD154 reagent used in these studies was provided by the NIH Nonhuman Primate Reagent Resource (R24 RR016001, N01 AI040101). The work was supported by Magee-Womens Research Institute and Foundation, The Richard King Mellon Foundation, NIH grants R01 HD055475 and R21 HD061289 to K.E.O., U54 HD008610 to Tony M. Plant and K.E.O., P01 HD047675 to G.P.S., and K99/R00 HD062687 to B.P.H. ",
year = "2012",
month = nov,
day = "2",
doi = "10.1016/j.stem.2012.07.017",
language = "English (US)",
volume = "11",
pages = "715--726",
journal = "Cell Stem Cell",
issn = "1934-5909",
publisher = "Cell Press",
number = "5",
}