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

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.

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.

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.

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.

These features indicate their suitability and safety for clinical application and underlay the importance of oxygen tension in preserving stem cell functionality.

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.