Systematic Intravenous Administration of Autologous Mesenchymal Stem Cells Is Safe

Background: Mesenchymal stem cells (MSCs) have drawn significant attention for their regenerative potential and therapeutic applicability across a range of conditions, including cardiovascular diseases and age-related frailty. Despite extensive preclinical studies, there remain gaps in understanding the long-term safety and efficacy of MSC therapy in humans. This study aimed to assess the safety of intravenous MSC administration, evaluate the mean major adverse cardiac and cerebrovascular event (MACCE)-free period, and identify potential risk factors for MACCE development in patients receiving MSC therapy for various indications. Methods: A retrospective observational study was conducted on 2504 patients (mean age: 54.09 ± 11.65 years) who received intravenous adipose-derived MSC (AD-MSC) therapy between October 2014 and December 2023 at the Omotesando Helene Clinic, Tokyo, Japan. Patients received MSC doses ranging from 100 million to 2 billion cells, with the majority receiving 1–2 billion cells per treatment. Statistical analyses included multivariate Cox proportional hazards regression and Kaplan–Meier survival analysis to evaluate MACCE risk factors and event-free duration. Results: Over the follow-up period, the MACCE rate was exceptionally low at 0.2%. Multivariate analysis identified age as a significant risk factor for MACCE (hazard ratio: 1.127; 95% CI: 1.0418–1.219; p = 0.0029), while sex and MSC dose showed no significant association. Minor adverse events occurred in 0.8% of patients, with no severe adverse events reported. The study found MSC therapy to be safe, with a low adverse event rate and minimal risk of MACCE. Conclusions: This study demonstrates the safety of intravenous MSC therapy in a large cohort of patients, with a low incidence of MACCE and minimal adverse effects. Age was the only significant predictor of MACCE risk. Further prospective randomized studies are needed to validate these findings and explore the potential of MSC therapy in reducing MACCE risk and improving clinical outcomes across diverse indications.