MP27-10 CRISPRA-ENGINEERED ADIPOSE-DERIVED STEM CELLS IMPROVE ERECTILE DYSFUNCTION IN DIABETIC RATS

Abstract

You have accessJournal of UrologyCME1 Apr 2023MP27-10 CRISPRA-ENGINEERED ADIPOSE-DERIVED STEM CELLS IMPROVE ERECTILE DYSFUNCTION IN DIABETIC RATS Wenchao Xu, Hao Li, Taotao Sun, Jiaxin Wang, Tao Wang, and Jihong Liu Wenchao XuWenchao Xu More articles by this author , Hao LiHao Li More articles by this author , Taotao SunTaotao Sun More articles by this author , Jiaxin WangJiaxin Wang More articles by this author , Tao WangTao Wang More articles by this author , and Jihong LiuJihong Liu More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003255.10AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Due to the high incidence of diabetes mellitus (DM) and poor response to phosphodiesterase type 5 inhibitor in DM-induced erectile dysfunction (DMED) patients, new therapeutic strategies for DMED are needed. Adipose-derived stem cells (ADSCs) transplantation is considered a promising treatment for DMED but is limited by poor survival and efficacy after transplantation. This study explored the therapeutic effect of CRISPRa-engineered ADSCs overexpressing GPX4 (GPX4-ADSCs) on erectile function in diabetic rats. METHODS: Thirty-two SD rats were randomly divided into four groups: the control, DMED, ADSCs, GPX4-ADSCs groups. Among them, the control group rats were non-diabetic rats, and the latter four groups were all diabetic ED rats of the same age. CRISPRa system was used to overexpress GPX4 in ADSCs. The GPX4-ADSCs group was treated with intracavernous injections of GPX4-ADSCs, while the ADSCs group was treated with ADSCs. Four weeks after transplantation, intracavernous pressure (ICP) and mean arterial pressure (MAP) were measured by electrical stimulation of cavernous nerve, and penile tissue was collected for subsequent testing. RESULTS: ADSCs and GPX4-ADSCs transplantation did not affect the weight or the glucose levels of diabetic rats. Although both the ADSCs group and the GPX4-ADSCs group improved erectile function in diabetic rats, the GPX4-ADSCs group had better improvement than the ADSCs group. In the DMED group, oxidative levels in the corpus cavernosum increased, PI3K/AKT/eNOS signal expression was down-regulated, Caspase3 activity was enhanced, and TGFβ1-Smad2/3-Collagen IV pathway was upregulated, showing obvious oxidative stress, apoptosis and fibrosis. ADSCs and GPX4-ADSCs can reverse these changes caused by diabetes to some extent, and GPX4-ADSCs are more effective than ADSCs. CONCLUSIONS: The CRISPRa-engineered ADSCs overexpressing GPX4 had stronger efficacy in improving erectile function than ADSCs, and the mechanism may involve reducing oxidative stress, apoptosis, and fibrosis, which provides a new strategy for the treatment of DMED. Source of Funding: This research was funded by grants from the National Natural Science Foundation of China (No. 82001536 and No.81873831) and the Fundamental Research Funds for the Central Universities (HUST: YCJJ202201021) © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e366 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Wenchao Xu More articles by this author Hao Li More articles by this author Taotao Sun More articles by this author Jiaxin Wang More articles by this author Tao Wang More articles by this author Jihong Liu More articles by this author Expand All Advertisement PDF downloadLoading ...