The promise of mesenchymal stromal/stem cells in erectile dysfunction treatment: a review of current insights and future directions

Abstract

Erectile dysfunction is a common and multifactorial condition that significantly impacts men's quality of life. Traditional treatments, such as phosphodiesterase type 5 inhibitors (PDE5i), often fail to provide lasting benefits, particularly in patients with underlying health conditions. In recent years, regenerative medicine, particularly stem cell therapies, has emerged as a promising alternative for managing erectile dysfunction. This review explores the potential of mesenchymal stromal/stem cells (MSCs) and their paracrine effects, including extracellular vesicles (EVs), in the treatment of erectile dysfunction. MSCs have shown remarkable potential in promoting tissue repair, reducing inflammation, and regenerating smooth muscle cells, offering therapeutic benefits in models of erectile dysfunction. Clinical trials have demonstrated positive outcomes in improving erectile function and other clinical parameters. This review highlights the promise of MSC therapy for erectile dysfunction, discusses existing challenges, and emphasizes the need for continued research to refine these therapies and improve long-term patient outcomes.

Keywords: Erectile dysfunction; Exosomes; MSCs; Male infertility; Regeneration; Stem cell therapy.

Fig. 1

Role of PRDX2 in enhancing the viability and functionality of ADMSCs and corpus cavernosum smooth muscle cells under oxidative and ferroptotic stress. PRDX2 overexpression in ADMSCs improves cell viability by reducing apoptosis and ROS levels in H2O2-stimulated cells. Additionally, PRDX2 alleviates oxidative stress and ferroptosis in H2O2- and RSL3-stimulated corpus cavernosum smooth muscle cells by decreasing ROS, total iron content, and MDA, while increasing SOD activity, GSH levels, and GPX4 expression, and reducing ACSL4 expression

Fig. 2

Therapeutic effects of SDF-1-engineered MSCs on erectile dysfunction in a diabetic rat model. SDF-1-engineered MSCs improved erectile function by increasing smooth muscle content and upregulating nNOS, eNOS, VEGF, and bFGF in the corpus cavernosum. VEGF-induced activation of the PI3K-AKT pathway enhanced cell survival by increasing Bcl-2 and reducing Bax levels, promoting the viability and functionality of transplanted MSCs

Fig. 3

Role of PDCD4 and miR-21-5p in regulating corpus cavernosum smooth muscle cell apoptosis and proliferation in diabetic erectile dysfunction. Elevated PDCD4 expression in diabetic rat cavernous tissue promotes apoptosis, while miR-21-5p, delivered via MSC-derived extracellular vesicles (EVs), inhibits PDCD4 activity. Suppression of PDCD4 results in increased Bax expression and decreased BCL-2 and PCNA levels, enhancing smooth muscle cell proliferation and reducing apoptosis under high-glucose conditions