Mesenchymal Stem Cells From a Klinefelter Syndrome Patient: Functional Characterization and Therapeutic Implications

BACKGROUND: Cell therapy, particularly those utilizing mesenchymal stem/stromal cells (MSCs), is gaining traction as a therapeutic option for regenerative treatment in patients with limited therapeutic options. Although the safety of MSC-based interventions is well established, uncertainties remain regarding how genetic abnormalities and culture conditions may influence their therapeutic efficacy. Klinefelter syndrome (KS; 47, XXY), the most common sex chromosome aneuploidy in males, is characterized by hypogonadism, infertility, and systemic comorbidities; however, its implications for autologous MSC-based interventions remain largely unexplored. OBJECTIVES: In this study, we isolated and characterized MSCs derived from the Wharton's jelly of an individual with KS (WJ-MSCs_KS) to evaluate their functional properties and therapeutic relevance. MATERIALS AND METHODS: A comprehensive in vitro and in vivo analysis was conducted, including assessments of morphology, proliferation, mesodermal tri-lineage differentiation capacity, senescence, expression of pluripotency, tumor suppressor, and senescence-associated markers, tumorigenicity in vivo, secretome profiling, neuroprotective properties, and endothelial differentiation potential of cells cultured under 21% O₂ and 5% of O₂. RESULTS: Our findings demonstrate that WJ-MSCs_KS exhibit functional, therapeutic and safety profiles that align with results reported for MSCs derived from healthy donors. Furthermore, culture under physiological normoxia (5% O₂) promoted proliferation and attenuated cellular senescence. DISCUSSION: These features indicate their suitability and safety for clinical application and underlay the importance of oxygen tension in preserving stem cell functionality. CONCLUSION: These results offer novel insights into the feasibility of autologous MSCs therapy in KS patients and highlight the relevance of personalized and optimized culture conditions for improving regenerative outcomes.