Abstract
Neonatal hypoxic-ischaemic encephalopathy (HIE) is a serious condition; many survivors develop neurological impairments, including cerebral palsy and intellectual disability. Preclinical studies show that the systemic administration of umbilical cord blood cells (UCBCs) is beneficial for neonatal HIE. We conducted a single-arm clinical study to examine the feasibility and safety of intravenous infusion of autologous UCBCs for newborns with HIE. When a neonate was born with severe asphyxia, the UCB was collected, volume-reduced, and divided into three doses. The processed UCB was infused at 12–24, 36–48, and 60–72 hours after the birth. The designed enrolment was six newborns. All six newborns received UCBC therapy strictly adhering to the study protocol together with therapeutic hypothermia. The physiological parameters and peripheral blood parameters did not change much between pre- and postinfusion. There were no serious adverse events that might be related to cell therapy. At 30 days of age, the six infants survived without circulatory or respiratory support. At 18 months of age, neurofunctional development was normal without any impairment in four infants and delayed with cerebral palsy in two infants. This pilot study shows that autologous UCBC therapy is feasible and safe.
Highlights
Neonatal hypoxic-ischaemic encephalopathy (HIE) is a serious condition; many survivors develop neurological impairments, including cerebral palsy and intellectual disability
We demonstrated that the intravenous infusion of human CD34+ cells at 48 hours after brain injury partially ameliorated the damage in mouse models of neonatal stroke[18] and neonatal HIE22
We have demonstrated that intraperitoneal infusion of the mononuclear cell (MNC) fraction of human umbilical cord blood cells (UCBCs) at 6 hours after brain injury partially ameliorates the damage in a rat model of neonatal HIE19
Summary
Neonatal hypoxic-ischaemic encephalopathy (HIE) is a serious condition; many survivors develop neurological impairments, including cerebral palsy and intellectual disability. At 18 months of age, neurofunctional development was normal without any impairment in four infants and delayed with cerebral palsy in two infants This pilot study shows that autologous UCBC therapy is feasible and safe. Preclinical studies with animal models with neonatal encephalopathy show that cell therapies initiated hours or days after the injury are beneficial. A variety of cell therapies have been reported as effective in preclinical studies, intravenous infusion of autologous (from the patient) umbilical cord blood cells (UCBCs) is currently regarded as the optimal cell therapy for newborns with HIE considering feasibility and safety[9,10]. We have demonstrated that intraperitoneal infusion of the MNC fraction of human UCBCs at 6 hours after brain injury partially ameliorates the damage in a rat model of neonatal HIE19. Regarding the intravenous infusion of autologous UCBCs for newborns with neonatal HIE, two clinical studies (NIH ClinicalTrials.gov website; NCT00593242, NCT01506258) apart from our study have been completed, and only one of these studies, which was conducted in the U.S, has been published[26]
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