Long-term safety of intravenous human umbilical cord blood-derived mesenchymal stem cell therapy in rheumatoid arthritis: a 5-year follow-up study.

Mesenchymal stem cell (MSC) therapy offers promise for treating autoimmune diseases due to its strong immunomodulatory effects. We investigated the long-term safety of a single intravenous injection with human umbilical cord blood-derived (hUCB)-MSCs in patients with rheumatoid arthritis (RA). Patients with RA who met the 2010 ACR/EULAR classification criteria and received a single intravenous infusion of hUCB-MSCs (2.5 × 107, 5.0 × 107, 1.0 × 108 cells) in a phase I trial (NCT02221258) entered this 5-year observational pilot study. Safety assessments were performed at 3, 6, and 12 months after infusion and annually thereafter. Safety endpoints included overall adverse events (AEs), serious adverse events (SAEs), and AEs of special interest. Nine patients were treated. The most common AEs were osteoarthritis (44.4%) and nasopharyngitis (44.4%). SAEs occurred in 5 patients (55.6%); a serious infection (cellulitis) occurred in 1 patient in the 1.0 × 108 group and resolved after treatment. Benign ovarian and breast tumors were reported in 2 patients 3 years post-infusion. No deaths, thromboembolism, or malignancies occurred during the follow-up period. Laboratory findings remained stable except for 1 case each of transient hypertriglyceridemia and mild eosinophilia. While DAS28 improved markedly by 3-6 months, disease activity gradually increased over 5 years, suggesting waning efficacy after a single infusion. The long-term safety profile of a single dose of intravenous hUCB-MSC in patients with RA appears acceptable; however, repeated-dose regimens may be needed for sustained disease control and further safety evaluation.