{
  "abstract": "Introduction Bronchopulmonary dysplasia (BPD) remains a major complication among extremely low gestational age (ELGA) infants, with long-term respiratory and neurodevelopmental consequences. Despite advances in neonatal care, effective therapies to prevent BPD are lacking. Mesenchymal stromal cells (MSCs), particularly those derived from umbilical cord (UC-MSC), offer promise due to their pleiotropic effects. Preclinical and early-phase clinical studies have demonstrated safety and potential efficacy of MSC in neonatal lung injury. The Helping Underdeveloped Lungs with Cells (HULC)-2 trial aims to evaluate whether multiple intravenous doses of human allogenic UC-MSC can reduce mechanical ventilation duration and improve the respiratory outcome in ELGA infants at high risk of developing BPD.Methods and analysis HULC-2 is a multicentre, double-blind, randomised controlled Phase II trial conducted in Canadian Neonatal Intensive Care Units. ELGA infants (gestational age <28 weeks) who remain ventilator-dependent between 4 and 14 days of life will be randomised to receive either 3 weekly intravenous doses of UC-MSC (10×10 6 cells/kg/dose) or a sham procedure. The primary outcome is ventilation-free days (VFDs) at 120 days postrandomisation, accounting for mortality. Secondary outcomes include cell administration safety, respiratory and neurodevelopmental outcomes and complications of prematurity. A total of 168 participants will be enrolled to detect a clinically meaningful difference in VFDs.Ethics and dissemination The study was approved through Clinical Trials Ontario by the Ottawa Health Science Network Research Ethics Board. Results will be disseminated via peer-reviewed publications, conferences and public engagement platforms. Parent partners are actively involved in study design and dissemination to ensure relevance and transparency.Trial registration number NCT07058025.",
  "authors": [
    {
      "affiliations": [
        "Pediatrics, Children’s Hospital of Eastern Ontario, Ottawa, Ontario, Canada",
        "Regenerative Medicine, The Ottawa Hospital Research Institute, Ottawa, Ontario, Canada",
        "University of Ottawa Faculty of Medicine, Ottawa, Ontario, Canada"
      ],
      "name": "Laurent Renesme"
    },
    {
      "affiliations": [
        "Pediatrics, Children’s Hospital of Eastern Ontario, Ottawa, Ontario, Canada",
        "Regenerative Medicine, The Ottawa Hospital Research Institute, Ottawa, Ontario, Canada",
        "University of Ottawa Faculty of Medicine, Ottawa, Ontario, Canada",
        "Children’s Hospital of Eastern Ontario Research Institute, Ottawa, Ontario, Canada"
      ],
      "name": "Emanuela Ferretti"
    },
    {
      "affiliations": [
        "Regenerative Medicine, The Ottawa Hospital Research Institute, Ottawa, Ontario, Canada",
        "Children’s Hospital of Eastern Ontario Research Institute, Ottawa, Ontario, Canada"
      ],
      "name": "Chantal Horth"
    },
    {
      "affiliations": [
        "Regenerative Medicine, The Ottawa Hospital Research Institute, Ottawa, Ontario, Canada",
        "Children’s Hospital of Eastern Ontario Research Institute, Ottawa, Ontario, Canada"
      ],
      "name": "Rebecca Grimwood"
    },
    {
      "affiliations": [
        "Regenerative Medicine, The Ottawa Hospital Research Institute, Ottawa, Ontario, Canada",
        "Children’s Hospital of Eastern Ontario Research Institute, Ottawa, Ontario, Canada"
      ],
      "name": "Liam Da Sylva"
    },
    {
      "affiliations": [
        "Regenerative Medicine, The Ottawa Hospital Research Institute, Ottawa, Ontario, Canada",
        "Children’s Hospital of Eastern Ontario Research Institute, Ottawa, Ontario, Canada"
      ],
      "name": "Viviane Olson"
    },
    {
      "affiliations": [
        "Regenerative Medicine, The Ottawa Hospital Research Institute, Ottawa, Ontario, Canada"
      ],
      "name": "Chanele Cyr-Depauw"
    },
    {
      "affiliations": [
        "Good Manufacturing Practice Facility, Center for Regenerative Therapies Dresden, Technische Universität Dresden, Dresden, Germany"
      ],
      "name": "Daniel Freund"
    },
    {
      "affiliations": [
        "Neonatology and Pediatric Intensive Care, University Hospital Carl Gustav Carus, Dresden, SN, Germany"
      ],
      "name": "Mario Rüdiger"
    },
    {
      "affiliations": [
        "Good Manufacturing Practice Facility, Center for Regenerative Therapies Dresden, Technische Universität Dresden, Dresden, Germany",
        "Neonatology and Pediatric Intensive Care, University Hospital Carl Gustav Carus, Dresden, SN, Germany"
      ],
      "name": "Marius A Möbius"
    },
    {
      "affiliations": [
        "Regenerative Medicine, The Ottawa Hospital Research Institute, Ottawa, Ontario, Canada"
      ],
      "name": "Samantha Hodgins"
    },
    {
      "affiliations": [
        "Regenerative Medicine, The Ottawa Hospital Research Institute, Ottawa, Ontario, Canada"
      ],
      "name": "Saad Khan"
    },
    {
      "affiliations": [
        "Regenerative Medicine, The Ottawa Hospital Research Institute, Ottawa, Ontario, Canada",
        "University of Ottawa Faculty of Medicine, Ottawa, Ontario, Canada"
      ],
      "name": "David Courtman"
    },
    {
      "affiliations": [
        "University of Ottawa Faculty of Medicine, Ottawa, Ontario, Canada",
        "The Ottawa Hospital Research Institute, Ottawa, Ontario, Canada"
      ],
      "name": "Dean A Fergusson"
    },
    {
      "affiliations": [
        "Pediatrics, Children’s Hospital of Eastern Ontario, Ottawa, Ontario, Canada",
        "Regenerative Medicine, The Ottawa Hospital Research Institute, Ottawa, Ontario, Canada",
        "University of Ottawa Faculty of Medicine, Ottawa, Ontario, Canada",
        "Children’s Hospital of Eastern Ontario Research Institute, Ottawa, Ontario, Canada"
      ],
      "name": "Bernard Thebaud"
    }
  ],
  "title": "Helping Underdeveloped Lungs with Cells (HULC-2): mesenchymal stromal cells in extreme preterm infants at risk of developing bronchopulmonary dysplasia – a study protocol of a phase 2 multicentre double blind randomised controlled trial in Canada",
  "uid": "66c8551e-d0fa-519c-9d41-afeb3c529b1d"
}