Mesenchymal stem cells for bronchopulmonary dysplasia: phase 1 dose-escalation clinical trial

J Pediatr. 2014 May;164(5):966-972.e6. doi: 10.1016/j.jpeds.2013.12.011. Epub 2014 Feb 6.


Objective: To assess the safety and feasibility of allogeneic human umbilical cord blood (hUCB)-derived mesenchymal stem cell (MSC) transplantation in preterm infants.

Study design: In a phase I dose-escalation trial, we assessed the safety and feasibility of a single, intratracheal transplantation of hUCB-derived MSCs in preterm infants at high risk for bronchopulmonary dysplasia (BPD). The first 3 patients were given a low dose (1 × 10(7) cells/kg) of cells, and the next 6 patients were given a high dose (2 × 10(7) cells/kg). We compared their adverse outcomes, including BPD severity, with those of historical case-matched comparison group.

Results: Intratracheal MSC transplantation was performed in 9 preterm infants, with a mean gestational age of 25.3 ± 0.9 weeks and a mean birth weight of 793 ± 127 g, at a mean of 10.4 ± 2.6 days after birth. The treatments were well tolerated, without serious adverse effects or dose-limiting toxicity attributable to the transplantation. Levels of interleukin-6, interleukin-8, matrix metalloproteinase-9, tumor necrosis factor α, and transforming growth factor β1 in tracheal aspirates at day 7 were significantly reduced compared with those at baseline or at day 3 posttransplantation. BPD severity was lower in the transplant recipients, and rates of other adverse outcomes did not differ between the comparison group and transplant recipients.

Conclusion: Intratracheal transplantation of allogeneic hUCB-derived MSCs in preterm infants is safe and feasible, and warrants a larger and controlled phase II study.

Trial registration: NCT01297205.

Publication types

  • Clinical Trial, Phase I

MeSH terms

  • Biomarkers / metabolism
  • Bronchopulmonary Dysplasia / diagnosis
  • Bronchopulmonary Dysplasia / metabolism
  • Bronchopulmonary Dysplasia / prevention & control*
  • Cord Blood Stem Cell Transplantation / adverse effects
  • Cord Blood Stem Cell Transplantation / methods*
  • Cytokines / metabolism
  • Feasibility Studies
  • Female
  • Hepatocyte Growth Factor / metabolism
  • Humans
  • Infant, Newborn
  • Infant, Premature
  • Logistic Models
  • Male
  • Mesenchymal Stem Cell Transplantation / adverse effects
  • Mesenchymal Stem Cell Transplantation / methods*
  • Severity of Illness Index
  • Trachea / metabolism
  • Trachea / surgery
  • Transplantation, Homologous / adverse effects
  • Transplantation, Homologous / methods
  • Treatment Outcome
  • Vascular Endothelial Growth Factor A / metabolism


  • Biomarkers
  • Cytokines
  • HGF protein, human
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • Hepatocyte Growth Factor

Associated data