Safety and preliminary efficacy of multiple intravenous infusions of human umbilical cord-derived mesenchymal stromal cells in idiopathic pulmonary fibrosis: a phase I dose-escalation trial

Background Idiopathic pulmonary fibrosis (IPF) is a progressive disease with limited therapeutic options. Mesenchymal stromal cells (MSCs) have shown promise in preclinical models of lung fibrosis. Methods We conducted an open-label, multicenter, dose-escalation phase I trial (NCT06230822) to assess the safety and preliminary efficacy of intravenous human umbilical cord-derived MSCs (UC-MSCs; VUM02) in patients with IPF. Nine patients were enrolled in three dose cohorts (0.5, 1.0, and 2.0 × 10⁸ cells per infusion, three infusions every 3 days) following a “3 + 3” design. Results No dose-limiting toxicities occurred. Seventy-four adverse events were recorded, most grade 1–2; only 13 events in four patients were considered possibly or probably related to UC-MSCs. Six serious adverse events occurred in five patients, all deemed unrelated to the investigational product. In the high-dose cohort, forced vital capacity (FVC) showed a numerical increase of 57 mL (+ 2.36%) at week 24 compared with baseline. Carbon monoxide diffusion capacity (DLCO % predicted) increased by 7.39% in the low-dose cohort at week 24. Exploratory immunological and plasma proteomic analyses suggested immunomodulatory effects and identified ribosomal protein S23 (RPS23) as a candidate biomarker that consistently decreased after treatment. Conclusions Multiple intravenous infusions of UC-MSCs up to 2 × 10⁸ cells were well tolerated in patients with IPF. Preliminary efficacy signals, particularly the numerical FVC improvement in the high-dose group, warrant further investigation in larger controlled trials. Trial registration: ClinicalTrials.gov NCT06230822.