Nanocarriers of Fertility: Mesenchymal Stem Cell-Derived Exosomes in Male Reproductive Repair

Male infertility is a multifactorial condition affecting approximately 8%-12% of reproductive-age couples worldwide, with male factors contributing to nearly half of all cases. Traditional treatments often offer limited efficacy, especially in cases involving testicular toxicity, diabetes-related erectile dysfunction, and aging-associated reproductive decline. In recent years, mesenchymal stem cell-derived exosomes (MSC-EXOS) have emerged as a promising cell-free therapeutic approach due to their ability to carry bioactive molecules-such as proteins, lipids, and microRNAs-that modulate inflammation, oxidative stress, apoptosis, and tissue regeneration. This review highlights the pathophysiology of key male reproductive disorders and explores the therapeutic potential of MSC-EXOS in preclinical models. Evidence demonstrates that exosomes from adipose tissue, bone marrow, and umbilical cord MSCs can improve spermatogenesis, restore hormonal balance, enhance vascular function, and repair damaged testicular architecture. While findings are encouraging, challenges remain regarding optimal delivery, dosage, and translation to clinical settings. This review provides the most comprehensive synthesis of preclinical evidence to date demonstrating that mesenchymal stem cell-derived exosomes consistently outperform traditional MSC therapy across multiple male reproductive disorders while offering superior safety and scalability. These findings establish exosomes as a transformative cell-free platform ready for clinical translation in male infertility, warranting further investigation through clinical trials and mechanistic studies.