hUC-MSCs safe and well-tolerated in mild-to-moderate ARDS, middle dose significantly improves oxygenation

Acute Respiratory Distress Syndrome (ARDS) remains a critical illness characterized by severe lung inflammation, high mortality, and limited specific therapeutic options. Current standard-of-care primarily offers supportive measures, failing to address the underlying inflammatory cascade and lung injury effectively. Mesenchymal stem cells (MSCs), particularly those derived from human umbilical cord (hUC-MSCs), are being investigated for their potent immunomodulatory and pro-reparative properties, offering a promising avenue to mitigate inflammation and restore tissue function in the ARDS microenvironment.

This open-label, multicenter Phase I clinical trial enrolled 12 eligible patients with mild-to-moderate ARDS into three dose groups using a "3 + 3" dose-escalation design. All patients received standard ARDS care alongside a single intravenous infusion of BC-U001 (allogeneic hUC-MSCs). Patients were followed for 28 days to assess primary endpoints of safety and tolerability, as well as preliminary efficacy. Exploratory analyses included immunological indicators such as immunoglobulins, inflammatory cytokines, and lymphocyte subsets to understand the mechanistic effects.

The trial observed no dose-limiting toxicity, treatment-related severe adverse events (SAE), or Suspected Unexpected Serious Adverse Reactions (SUSAR) across all dose groups, demonstrating excellent safety and tolerability. The overall 28-day all-cause mortality rate was 8.3% (1/12), with 0% mortality reported among the 5 patients with COVID-19-related ARDS. Efficacy analysis revealed significant improvements, particularly in the middle dose group:

Oxygenation index (PaO2/FiO2) increased by +100.07 mmHg (P < 0.001), and PaO2 increased by +21.88 mmHg (P = 0.002). Significant reductions were also noted in Lung Injury Score (LIS), Sequential Organ Failure Assessment (SOFA), and Acute Physiology and Chronic Health Evaluation (APACHE) II scores, although these effects did not exhibit a clear dose-dependent pattern. Exploratory analyses suggested that hUC-MSCs modulated the inflammatory response and helped restore immune balance.