The safety and efficacy of human umbilical cord mesenchymal stem cell for acute respiratory distress syndrome: an open-label and multicenter phase 1 clinical trial

Trial design Acute Respiratory Distress Syndrome (ARDS) remains a life-threatening critical illness with high mortality and limited specific therapies. This open-label, multicenter Phase I clinical trial aimed to evaluate the safety, tolerability, and preliminary efficacy of allogeneic human umbilical cord mesenchymal stem cells (hUC-MSCs, BC-U001) in patients with mild-to-moderate ARDS. A total of 12 eligible patients were enrolled into three dose groups following a “3 + 3” dose-escalation design from 2019 to 2024. Methods All patients received standard ARDS care plus a single intravenous infusion of BC-U001, with 28-day follow-up to assess safety and efficacy as well as exploratory immunological indicators (immunoglobulins, inflammatory cytokines, lymphocyte subsets). Results Baseline characteristics were balanced across groups except for more severe baseline lung injury in high dose patients ( P = 0.027 ). No dose-limiting toxicity, treatment-related severe adverse events (SAE), or Suspected Unexpected Serious Adverse Reactions (SUSAR) were observed across all dose groups. The overall 28-day all-cause mortality rate was 8.3% (1/12), with 0% mortality among 5 COVID-19-related ARDS patients. Efficacy analysis showed significant improvements in the middle dose group, including a marked increase in PaO 2 /FiO 2 (+100.07 mmHg, P < 0.001 ) and PaO 2 (+21.88 mmHg, P = 0.002 ), as well as significant reductions in Lung Injury Score (LIS), Sequential Organ Failure Assessment (SOFA), and Acute Physiology and Chronic Health Evaluation (APACHE) II scores, without dose-dependent effects observed. Exploratory analyses preliminarily revealed that hUC-MSCs modulated the inflammatory response and restored immune balance. Conclusions These findings demonstrate that hUC-MSCs are safe and well-tolerated in mild-to-moderate ARDS patients, with the middle dose showing promising therapeutic effects. This trial provides critical data to support the design of future large-scale, randomized controlled trials to confirm the efficacy of hUC-MSCs for ARDS.