MicroRNA-145 Gene Modification Enhances the Retention of Bone Marrow-Derived Mesenchymal Stem Cells within Corpus Cavernosum by Targeting Krüppel-Like Factor 4

Daoyuan Hu; Yunlong Ge; Yuhang Xi; Jialiang Chen; Hua Wang; Chi Zhang; Yubin Cui; Lizhao He; Ying Su; Jun Chen; Cheng Hu; Hengjun Xiao

doi:10.5534/wjmh.230149

MicroRNA-145 Gene Modification Enhances the Retention of Bone Marrow-Derived Mesenchymal Stem Cells within Corpus Cavernosum by Targeting Krüppel-Like Factor 4

World J Mens Health. 2024 Jan 2. doi: 10.5534/wjmh.230149. Online ahead of print.

Authors

Daoyuan Hu^{1

2}, Yunlong Ge¹, Yuhang Xi¹, Jialiang Chen¹, Hua Wang¹, Chi Zhang¹, Yubin Cui¹, Lizhao He¹, Ying Su³, Jun Chen³, Cheng Hu⁴, Hengjun Xiao⁵

Affiliations

¹ Department of Urology, The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.
² Department of Urology, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.
³ Department of Infertility and Sexual Medicine, The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.
⁴ Department of Urology, The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China. hucheng2@mail.sysu.edu.cn.
⁵ Department of Urology, The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China. xiaohjun@mail.sysu.edu.cn.

PMID: 38164035
DOI: 10.5534/wjmh.230149

Abstract

Purpose: The poor retention and ambiguous differentiation of stem cells (SCs) within corpus cavernosum (CC) limit the cell application in erectile dysfunction (ED). Herein, the effects and mechanism of microRNA-145 (miR-145) gene modification on modulating the traits and fate of bone marrow-derived mesenchymal stem cells (BMSCs) were investigated.

Materials and methods: The effects of miR-145 on cell apoptosis, proliferation, migration, and differentiation were determined by flow cytometry, cell counting kit-8, transwell assays and myogenic induction. Then, the age-related ED rats were recruited to four groups including phosphate buffer saline, BMSC, vector-BMSC, overexpressed-miR-145-BMSC groups. After cell transplantation, the CC were harvested and prepared to demonstrate the retention and differentiation of BMSCs by immunofluorescent staining. Then, the target of miR-145 was verified by quantitative real-time polymerase chain reaction and immunohistochemical. After that, APTO-253, as an inducer of Krüppel-like factor 4 (KLF4), was introduced for rescue experiments in corpus cavernosum smooth muscle cells (CCSMCs) under the co-culture system.

Results: In vitro, miR-145 inhibited the migration and apoptosis of BMSCs and promoted the differentiation of BMSCs into smooth muscle-like cells with stronger contractility. In vivo, the amount of 5-ethynyl-2'-deoxyuridine (EdU)⁺cells within CC was significantly enhanced and maintained in the miR-145 gene modified BMSC group. The EdU/CD31 co-staning was detected, however, no co-staining of EdU/α-actin was observed. Furthermore, miR-145, which secreted from the gene modified BMSCs, dampened the expression of KLF4. However, the effects of miR-145 on CCSMCs could be rescued by APTO-253.

Conclusions: Overall, miR-145 modification prolongs the retention of the transplanted BMSCs within the CC, and this effect might be attributed to the modulation of the miR-145/KLF4 axis. Consequently, our findings offer a promising and innovative strategy to enhance the local stem cell-based treatments.

Keywords: Apoptosis; Cell differentiation; Erectile dysfunction; MicroRNAs; Stem cells.

Abstract

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