A narrative review of the distribution and role of multipotent fibroblasts in penile tissue: implications for regenerative medicine and erectile dysfunction

초록

Background and Objective: Erectile dysfunction (ED) is a common male sexual disorder with multifactorial etiologies, including diabetes mellitus and cavernous nerve injury. Recent developments in single-cell RNA sequencing (scRNA-seq) have revealed substantial cellular heterogeneity within the corpus cavernosum, especially among fibroblast (FB) subclusters. This review aims to delineate the roles of these FB subclusters and their extracellular vesicles (EVs) in the pathogenesis and potential treatment of ED. Methods: A comprehensive literature review was conducted focusing on studies utilizing scRNAseq to analyze human and murine corpus cavernosum tissues under physiological and ED-associated conditions. Key findings regarding FB subcluster classification, transcriptomic landscapes, and intercellular communication were synthesized, with particular attention to the fibrotic and regenerative roles of FBderived EVs. Key Content and Findings: Distinct FB subclusters were identified, exhibiting profibrotic, regenerative, and signaling-related phenotypes. In ED models, including diabetes-and cavernous nerve injury-induced conditions, an increased prevalence of fibrotic FB phenotypes was observed, contributing to structural disruption and functional decline. FB-derived EVs were highlighted as pivotal mediators of paracrine signaling, influencing endothelial and smooth muscle cell function, modulating immune responses, and regulating extracellular matrix remodeling. Therapeutic administration of EVs demonstrated promising regenerative effects in preclinical ED models. Conclusions: FB subclusters and their EVs play central roles in the pathophysiology of ED, functioning in both deleterious and reparative capacities. Selective targeting of specific FB subpopulations or leveraging the therapeutic properties of FB-derived EVs may represent innovative strategies for managing ED, particularly in treatment-resistant cases.

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