First-In-Human Administration of Allogeneic Amnion Cells in Premature Infants With Bronchopulmonary Dysplasia: A Safety Study

Abstract

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

Human amnion epithelial cells and their soluble factors reduce liver fibrosis in murine non‐alcoholic steatohepatitis

“…We have begun phase 1 safety studies of hAEC in adult cirrhotic patients. Should these studies support the existing safety data on the human administration of hAECs to infants, 38 our findings should be replicated in adult patients with NASH, a condition with limited effective therapeutic options.…”

Two-year outcomes of infants enrolled in the first-in-human study of amnion cells for bronchopulmonary dysplasia

“…Six extremely preterm and ELBW infants (five boys, one girl) with a median (range) gestation at birth of 26 (24‐28) weeks and birth weight of 795 (450‐990) grams were administered hAECs at 89 (59‐187) postnatal days. One infant (baby 2) died a month after cell administration due to an unrelated cause . All five surviving infants were discharged home on supplemental low‐flow oxygen at a median of 174 (155‐388) days of life.…”

“…The methods to collect, prepare, and release hAECs have been detailed previously . In brief, placentae from healthy women with an uncomplicated pregnancy undergoing an elective cesarean section at term gestation were collected at the time of delivery.…”

“…All babies received the cells via a peripheral intravenous infusion. As previously described in detail, the first baby received the cell infusion by a slow, hand‐delivered injection. Subsequent babies received hAEC infusions delivered over 30 minutes by a syringe pump on a platform rocker.…”

“…16 We have previously reported the immediate and short-term outcomes until discharge from hospital. 16 The aim of this further report was to describe the longer term safety outcomes of the infants until age 2, as originally detailed in the clinical trial protocol (ACTRN12614000174684).…”