World J Mens Health.  2024 Oct;42(4):787-796. 10.5534/wjmh.230218.

Repeated Injections of Mesenchymal Stem CellDerived Exosomes Ameliorate Erectile Dysfunction in a Cavernous Nerve Injury Rat Model

Affiliations
  • 1Department of Urology, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
  • 2Catholic Prostate Institute, The Catholic University of Korea, Seoul, Korea
  • 3Cancer Research Institute, College of Medicine, The Catholic University of Korea, Seoul, Korea
  • 4Department of Biomedicine & Health Sciences, College of Medicine, The Catholic University of Korea, Seoul, Korea
  • 5Department of Mechanical Engineering, Pohang University of Science and Technology, Pohang, Korea

Abstract

Purpose
To evaluate the therapeutic effect of repeated injections of mesenchymal stem cell (MSC)-derived exosomes on the erectile dysfunction (ED) of bilateral cavernous nerve injury (BCNI) rat model and to identify potential target genes of these injections.
Materials and Methods
MSC-derived exosomes were isolated using an aqueous two-phase system. Rats were randomly assigned into four groups: Normal, BCNI, exosome once, and exosome-repeat groups. After four weeks, we measured the intracavernosal pressure (ICP)/mean arterial pressure (MAP) ratio to evaluate erectile function and examined cavernous nerve tissues for histological and molecular analyses. RNA sequencing in penile tissues was used to determine differentially expressed genes and was verified by quantitative polymerase chain reaction. Human umbilical vein endothelial cells (HUVECs) were used for in vitro studies to analyze biological roles.
Results
The ICP/MAP ratios in the exosome-once and exosome-repeat groups were significantly increased compared to those in the BCNI group. Interestingly, the ICP/MAP ratio showed a greater increase in the exosome-repeat group, which also showed significantly increased smooth muscle/collagen ratio, α-smooth muscle actin and neuronal nitric oxide synthase expression, and cyclic guanosine monophosphate level compared to the BCNI and exosome-once groups. Three genes were significantly differentially expressed in the exosome group, among which Ras homolog family member B promoted cell proliferation and angiogenesis of HUVECs.
Conclusions
Repeated injections of MSC-derived exosomes can be effective in the treatment of rat models with ED induced by cavernous nerve injury.

Keyword

Erectile dysfunction; Exosomes; Nerve injury; RhoB
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