First-In-Human Administration of Allogeneic Amnion Cells in Premature Infants With Bronchopulmonary Dysplasia: A Safety Study.
Rebecca LimAtul MalhotraJean L TanSiow Teng ChanSinnee LauDandan ZhuJoanne C MocklerEuan M WallacePublished in: Stem cells translational medicine (2018)
Bronchopulmonary dysplasia (BPD) is a chronic lung disease that mainly affects premature babies who require ventilator support. The pathogenesis of BPD is complex but includes vascular maldevelopment, alveolarization arrest, and lung inflammation. There is no cure for BPD. Clinical care is limited to supportive respiratory measures. A population of stem-like cells derived from placental membranes, human amnion epithelial cells (hAECs), has shown therapeutic promise in preclinical models of BPD. With a view to future efficacy trials, we undertook a first-in-human clinical trial of hAECs in babies with BPD to assess the safety of these cells. In a single-center, open-label phase I trial, we administered allogeneic hAECs (1 × 106 per kilogram bodyweight) by intravenous infusion to six premature babies with BPD. The primary outcomes of the study were focused on safety, including local site reaction, anaphylaxis, infection, features of rejection, or tumor formation. Outcomes to discharge from neonatal unit were studied. The hAECs were well tolerated. In the first baby, there was transient cardiorespiratory compromise during cell administration consistent with a pulmonary embolic event. Following changes to cell administration methods, including introduction of an inline filter, and reducing the cell concentration and the rate of cell infusion, no such events were observed in the subsequent five babies. We did not see evidence of any other adverse events related to cell administration. Allogeneic hAECs can be safely infused into babies with established BPD. Future randomized clinical trials to assess efficacy in this patient population are justified. Stem Cells Translational Medicine 2018;7:628-635.
Keyphrases
- cell therapy
- clinical trial
- single cell
- stem cells
- endothelial cells
- stem cell transplantation
- open label
- induced apoptosis
- low dose
- bone marrow
- healthcare
- randomized controlled trial
- palliative care
- gestational age
- study protocol
- phase ii
- intensive care unit
- squamous cell carcinoma
- oxidative stress
- cell cycle arrest
- mesenchymal stem cells
- case report
- signaling pathway
- type diabetes
- high dose
- machine learning
- blood brain barrier
- subarachnoid hemorrhage
- hematopoietic stem cell
- pulmonary hypertension
- skeletal muscle
- drug induced
- quality improvement
- weight loss
- radiation therapy
- extracorporeal membrane oxygenation
- brain injury
- mechanical ventilation
- chronic pain
- health insurance
- cell cycle