PD33-10 HUMAN INDUCED PLURIPOTENT STEM CELL-DERIVED TESTOSTERONE-PRODUCING LEYDIG CELLS AMELIORATE SERUM TESTOSTERONE LEVEL IN RATS.

Abstract

You have accessJournal of UrologyStem Cell Research: Stem Cell Research I1 Apr 2018PD33-10 HUMAN INDUCED PLURIPOTENT STEM CELL-DERIVED TESTOSTERONE-PRODUCING LEYDIG CELLS AMELIORATE SERUM TESTOSTERONE LEVEL IN RATS. Takaki Ishida, Mikito Tanaka, Kenta Sumii, Keisuke Okada, Koji Chiba, Kei Matsushita, Masato Fujisawa, and Takashi Aoi Takaki IshidaTakaki Ishida More articles by this author , Mikito TanakaMikito Tanaka More articles by this author , Kenta SumiiKenta Sumii More articles by this author , Keisuke OkadaKeisuke Okada More articles by this author , Koji ChibaKoji Chiba More articles by this author , Kei MatsushitaKei Matsushita More articles by this author , Masato FujisawaMasato Fujisawa More articles by this author , and Takashi AoiTakashi Aoi More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2018.02.1565AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Recently male late-onset hypogonadism syndrome (LOH syndrome) is focused on with various symptoms due to hypogonadism. Although the results of the differentiation instructions from human induced pluripotent stem cell (human iPS cells) to many various cells, there is no report that succeed in induced Leydig cell which secret androgens. In this time we succeeded in Induced Leydig cell secrete testosterone from human iPS cells. METHODS First, we transduced NR5A1 expressing system by doxycycline addition to human iPS cell. We examined various genetic expression and hormone producing ability and evaluate the differentiation instruction from this cell under a timing of the NR5A1 forced expression and various kinds of conditions. Human iPS cells-derived testosterone-producing Leydig cells were transplanted into castrated male rats and examined for improvement in serum testosterone levels. RESULTS Leydig cell marker (INSL3 variant2) and LH receptor (LHCGR) and Leydig cell-specific enzyme (17βHSD3)and expression of various enzyme (StAR,CYP11A,3βHSD2,CYP17A) necessary for testosterone production were confirmed in RT-PCR.INSL3 and LHCGR were confirmed in Immunohistochemical staining.Testosterone production was confirmed by the hormone measurement in supernatants. And we showed that transplantation of human iPS cells-derived testosterone-producing Leydig cells to castrated rats ameliorate serum testosterone levels.At the same time, expression of adrenal cortex-specific enzyme (CYP21A2,CYP11B1,CYP11B2) necessary for cortisol and aldosterone production were confirmed in RT-PCR. The cluster of Leydig cells include the adrenal cortex cells too. CONCLUSIONS We succeeded in Leydig cell instruction from human iPS cells. At the same time to adrenocortical cell is induced, and we will examine the specific differentiation instruction conditions to Leydig cell in future. Transplantation of human iPS cells-derived testosterone-producing Leydig cells to castrated rats ameliorate serum testosterone levels. © 2018FiguresReferencesRelatedDetails Volume 199Issue 4SApril 2018Page: e654 Advertisement Copyright & Permissions© 2018MetricsAuthor Information Takaki Ishida More articles by this author Mikito Tanaka More articles by this author Kenta Sumii More articles by this author Keisuke Okada More articles by this author Koji Chiba More articles by this author Kei Matsushita More articles by this author Masato Fujisawa More articles by this author Takashi Aoi More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...