Real-world safety profile of repeated outpatient autologous adipose-derived mesenchymal stromal cell therapy: a single-center registry of 2,212 administrations with 553.5 person-years of follow-up

Abstract Background Mesenchymal stromal cell (MSC) therapy is increasingly delivered in real-world outpatient settings, yet long-term safety data from longitudinal registries in high-comorbidity outpatient cohorts remain limited. Available evidence is dominated by short-duration phase 1/2 trials, with limited information on the safety of repeated MSC administration in routine practice. We addressed this gap through a longitudinal registry under Japan’s regenerative medicine framework. Methods We conducted a single-center retrospective observational registry of 449 consecutive patients receiving 2,212 outpatient autologous adipose-derived MSC administrations (April 2019–December 2025) under Japan’s Act on the Safety of Regenerative Medicine (23 approved Class II provision plans). Cells were manufactured on-site to release-target passage 4 using autologous serum-supplemented medium and administered on the day of manufacture via intravenous (IV), intra-arterial, intrathecal, and local-injection routes, alone or in combination. IV-containing sessions (approximately 89%) received prophylactic IV heparin (5,000 IU). Long-term follow-up used disease-specific evaluation databases enabling person-time–based analysis. Adverse events were graded by CTCAE v5.0; SAE rates were analyzed using exact Poisson bounds. Results Mean age was 61.5 years; 68.2% received ≥ 3 sessions. Longitudinal follow-up covered 408 of 449 patients (90.9%); cumulative person-time was 553.5 person-years. No serious adverse event occurred across 2,212 administrations under this specific protocol (upper 95% CI: 0.14% per administration; 5.42 per 1,000 person-years). No thromboembolic events, hospitalizations, or deaths attributable to therapy were observed. Minor adverse events were mild and self-limited. Safety findings are primarily applicable to IV-containing administrations under prophylactic heparinization; sample sizes for non-IV single-route administrations were smaller and interpreted as hypothesis-generating. Conclusions In a single-center registry of repeated outpatient autologous AT-MSC therapy under on-site same-day manufacture and standardized prophylactic heparinization for IV-containing sessions, no serious adverse events occurred across 2,212 administrations over 553.5 person-years. These findings are specific to the studied protocol and should not be extrapolated to other MSC products, routes, doses, or clinical indications. The observations support short- to intermediate-term safety of this specific protocol and provide a real-world translational benchmark that motivates, rather than replaces, prospective comparator-controlled and disease-specific safety studies.