Pd23-01 Implantation of Nr5a1-Induced Steroidogenic Cells Derived From Human Adipose Tissue-Derived Mesenchymal Stem/Stromal Cells Into Adrenal-Insufficiency Model Mice

You have accessJournal of UrologyAdrenal (PD23)1 May 2024PD23-01 IMPLANTATION OF NR5A1-INDUCED STEROIDOGENIC CELLS DERIVED FROM HUMAN ADIPOSE TISSUE-DERIVED MESENCHYMAL STEM/STROMAL CELLS INTO ADRENAL-INSUFFICIENCY MODEL MICE Chikao Aoyagi, Tomoko Tanaka, Toshihiko Yanase, Nobuhiro Haga, and Shohta Kodama Chikao AoyagiChikao Aoyagi , Tomoko TanakaTomoko Tanaka , Toshihiko YanaseToshihiko Yanase , Nobuhiro HagaNobuhiro Haga , and Shohta KodamaShohta Kodama View All Author Informationhttps://doi.org/10.1097/01.JU.0001008664.51020.58.01AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Cell therapy for adrenal insufficiency is a potential method for physiological glucocorticoid replacement. Nuclear receptor 5A1 (NR5A1) is an important transcriptional factor for steroidogenesis. We previously demonstrated that mouse mesenchymal stem/stromal cells (MSCs) were differentiated into steroid hormone-producing cells by overexpression of NR5A1, and syngeneic implantation of NR5A1-induced steroidogenic cells improved the survival of bilateral adrenalectomized mice. For clinical applications, it is necessary to reveal therapeutic effect of transplantation of human steroidogenic cells, not mouse steroidogenic cells. The aim of the present study is to investigate the potential of human MSCs as a regenerative source of steroidogenic cells. METHODS: Human adipose tissue-derived MSCs (ADSCs) were differentiated into steroidogenic cells by overexpression of NR5A1. We examined the adrenocorticotropic hormone (ACTH) and angiotensin II responsiveness in vitro and xeno-implanted human NR5A1-induced steroidogenic cells into immunodeficient bilateral adrenalectomized mice (bADX mice). RESULTS: Human NR5A1-induced steroidogenic cells produced both adrenal and gonadal steroids and responded to ACTH and angiotensin II in vitro. In long-term culture experiments, cortisol production of NR5A1-induced steroidogenic cells lasted for 28 days. In experimental implantation, the survival time of bADX mice implanted with NR5A1-inudced steroidogenic cells was significantly prolonged compared with that of bADX mice implanted with control cells (log-rank test, p<0.0001)(Figure 1). All mice implanted with control cells died within 13 days (n=10), whereas the survival rate of mice implanted with NR5A1-induced steroidogenic cells was 16.7% (n=12) on post-operative 30 days. Serum cortisol was detected in bADX mice implanted with NR5A1-induced steroidogenic cells, suggesting replacement from the xenograft. CONCLUSIONS: This is the first report to demonstrate steroid replacement by the transplantation of human steroidogenic cells derived from ADSCs. These results provide the potential utility of ADSCs in cell therapy for adrenal insufficiency. Download PPT Source of Funding: Nothing © 2024 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 211Issue 5SMay 2024Page: e523 Advertisement Copyright & Permissions© 2024 by American Urological Association Education and Research, Inc.Metrics Author Information Chikao Aoyagi More articles by this author Tomoko Tanaka More articles by this author Toshihiko Yanase More articles by this author Nobuhiro Haga More articles by this author Shohta Kodama More articles by this author Expand All Advertisement PDF downloadLoading ...