Human Umbilical Cord-Derived Mesenchymal Stem Cells for Acute Respiratory Distress Syndrome

Crit Care Med. 2020 May;48(5):e391-e399. doi: 10.1097/CCM.0000000000004285.


Objectives: To investigate the safety, feasibility, and possible adverse events of single-dose human umbilical cord-derived mesenchymal stem cells in patients with moderate-to-severe acute respiratory distress syndrome.

Design: Prospective phase I clinical trial.

Setting: Medical center in Kaohsiung, Taiwan.

Patients: Moderate-to-severe acute respiratory distress syndrome with a PaO2/FIO2 ratio less than 200.

Interventions: Scaling for doses was required by Taiwan Food and Drug Administration as follows: the first three patients received low-dose human umbilical cord-derived mesenchymal stem cells (1.0 × 10 cells/kg), the next three patients with intermediate dose (5.0 × 10 cells/kg), and the final three patients with high dose (1.0 × 10 cells/kg) between December 2017 and August 2019.

Measurements and main results: Nine consecutive patients were enrolled into the study. In-hospital mortality was 33.3% (3/9), including two with recurrent septic shock and one with ventilator-induced severe pneumomediastinum and subcutaneous emphysema. No serious prespecified cell infusion-associated or treatment-related adverse events was identified in any patient. Serial flow-cytometric analyses of circulating inflammatory biomarkers (CD14CD33/CD11b+CD16+/CD16+MPO+/CD11b+MPO+/CD14CD33+) and mesenchymal stem cell markers (CD26+CD45-/CD29+CD45-/CD34+CD45-/CD44+CD45-/CD73+CD45-/CD90+CD45-/CD105+CD45-/CD26+CD45-) were notably progressively reduced (p for trend < 0.001), whereas the immune cell markers (Helper-T-cell/Cytotoxity-T-cell/Regulatory-T-cell) were notably increased (p for trend < 0.001) after cell infusion.

Conclusions: The result of this phase I clinical trial showed that a single-dose IV infusion of human umbilical cord-derived mesenchymal stem cells was safe with favorable outcome in nine acute respiratory distress syndrome patients.

Publication types

  • Clinical Trial, Phase I
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Drug Dosage Calculations
  • Female
  • Hospital Mortality / trends
  • Humans
  • Male
  • Mesenchymal Stem Cell Transplantation / adverse effects
  • Mesenchymal Stem Cell Transplantation / methods*
  • Mesenchymal Stem Cell Transplantation / mortality
  • Mesenchymal Stem Cells / classification
  • Mesenchymal Stem Cells / physiology*
  • Middle Aged
  • Prospective Studies
  • Respiratory Distress Syndrome / mortality
  • Respiratory Distress Syndrome / therapy*
  • Severity of Illness Index
  • Umbilical Cord / physiology*

Associated data

  • ISRCTN/ISRCTN52319075