Discussion
tumour, necrosis
PAD, TUMOUR, COMPLICATIONS, NECROSIS
Our phase I clinical trial demonstrates that the implantation of autologous MPCs in combination with or without NMES for the treatment of SUI grade ≥I in women is safe and feasible. Therapy was well tolerated by patients and no relevant or unexpected AEs and no need for consecutive surgical or interventional treatments were documented (all complications Clavien–Dindo grade ≤II). Further, our analysis demonstrated an objective improvement of the median FUL under stress in the urodynamic study 6 months after injection of autologous MPCs into the EUS. In addition, PROMs evaluated by questionnaires improved with a lower median ICIQ-UI-SF score at 6 months after the intervention, suggesting a better quality of life in these patients. All patients with a positive 1-h pad test at baseline improved at follow-up with 2 out of 3 patients being completely dry. Finally, the analysis of the MRI of the pelvis revealed an increase in EUS diameter. Most importantly, no evidence of cell transformation (i.e. tumour tissue or necrosis) at the end of follow-up was found radiologically. The decrease in MUCP and FUL values at rest comparing from before with after treatment was not statistically significant. However, all results need to be further elucidated in larger patient cohorts during prospective phase II and III trials. To investigate the overall regenerative potential of this approach, patients are further included in a long-term follow-up study for the analysis of safety and efficacy up to 5 years after treatment.For more than two decades, there has been an immense research effort to ameliorate the treatment of SUI with a regenerative approach [Results from studies investigating other therapy approaches with transurethral injections of autologous MDSCs have shown them to be safe and feasible without any relevant AEs or SAEs. Dose-ranging studies using MDSCs (1–200 million cells) by Chancellor and his group [It is worth mentioning that different muscle-derived cell populations have shown a potentially different impact on functional regeneration and their modes of action—some through paracrine effects, others through direct integration into the damaged tissue. Importantly, the main therapeutic effect in our patient population is achieved by MPC-induced muscle regeneration of the EUS. The additional usage of NMES may be a potential advantage for an ameliorated functional outcome owing to additional growth stimulation through training of the pelvic musculature. However, a subgroup analysis to investigate the therapeutic effect of MPC + NMES vs MPC alone was not feasible in the underlying study owing to limited patient numbers. Altogether, all these results underline the potential of a regenerative therapy approach to the treatment of SUI in women.Our functional results need to be interpreted with caution as this was a phase I trial investigating solely safety and feasibility. Owing to the limited number of patients and the associated lack of statistical power, no subgroup analysis regarding the randomisation into MPC vs MPC + NMES was performed. Further, only 3 out of 9 patients had a positive 1-h pad test at baseline. Therefore, the efficacy and durability of the treatment need to be confirmed with larger patient cohorts and longer follow-up periods in specifically designed, accordingly powered and prospectively performed phase II and III trials.