Umbilical Cord-derived Mesenchymal Stem Cells (CLV-100) Infusion in Healthy Subjects: a 5-Year Follow-up Study on Safety and Immunomodulatory Effect

Purpose: Umbilical cord-derived mesenchymal stem cells (UCMSCs) have garnered significant attention in the field of regenerative medicine, specifically in inflammation-related diseases. Our team has previously demonstrated that a single infusion of allogeneic UCMSCs by Cytopeutics (R) (CLV-100), at both low dose (65 million cells) and high dose (130 million cells), in 11 healthy volunteers was safe up to 6 months with a dose-dependent immunomodulatory effect. In this present follow-up study, we investigated the medium-term safety and efficacy of intravenous administration of CLV-100 in the same healthy subjects. Methods: All 11 subjects were enrolled in this 5-year follow-up, and none dropped out (NMRR-13-1152-17400, 28/09/2016). Clinicians conducted consultations to assess overall health indicators. Blood samples and serum were collected for laboratory testing and biomarker analysis, respectively. Results: Five years after the CLV-100 infusion, all subjects remained healthy, with no reported side effects or major health conditions. Levels of cancer markers also remained within normal ranges. The anti-inflammatory effect of CLV-100 remained statistically significant in the high-dose group. Notably, major organ health parameters, including those subjects aged over 60 years, remained stable even after 5 years. Conclusion: The findings demonstrated the medium-term safety of a single CLV-100 infusion and persistent dose-dependent immunomodulatory effects. CLV-100 may also confer protection against age- and inflammation-related frailty. Lay Summary: The current follow-up study provides insight into the safety and immunomodulatory effects of a single infusion of allogeneic umbilical cord-derived mesenchymal stem cells (CLV-100) for up to 5 years in healthy subjects. The effects on the inflammatory cytokines CLV-100 were more pronounced in the high-dose group. In addition, other biomarker levels were comparable between the older and younger age groups. CLV-100 is therefore safe over the medium-term with sustained anti-inflammatory effect in a dose-dependent manner.