Clinical Assistant Professor Samsung Medical Center Gangnam, Seoul-t'ukpyolsi, Republic of Korea
Background: Stem cell researches have generated great interest in that attenuation of neonatal brain injury in the animal models as a promising approach for the treatment of HIE and IVH in the newborn infants. Previously, we reported that thrombin preconditioned human Wharton jelly derived MSCs (ThWJ-MSC) had therapeutic efficacy in animal models of IVH and HIE. Objective: We thus performed a phase 1 clinical trial to assess the safety and feasibility of ThWJ-MSC prophylactic therapy in newborn brain injury of HIE/IVH infants. Design/Methods: We obtained approval for a phase 1 clinical trial to explore the safety and feasibility of ThWJ-MSCs in two neonatal brain disorders, HIE and IVH based on the similar mechanisms of injury in these neonatal brain diseases (KCT0004851). For HIE, we included neonates with evidence of moderate to severe HIE who have started hypothermia therapy within 6 hours of birth, have a gestational age of at least 36 weeks, and a birth weight of more than 1,800 grams. These infants underwent 72 hours of hypothermia therapy and then received a single intraventricular injection of the experimental drug within 72 hours following the completion of this treatment. For IVH, we included neonates who were diagnosed within 7 days post-IVH diagnosis and within 28 days of birth, had a gestational age between 23 and less than 34 weeks, and were diagnosed with grade 3 - 4 IVH by a radiologist using brain sonography. The primary outcomes were the safety and feasibility of the intracerebroventricular injection of ThWJ-MSCs (5x106cells/kg-1x107cells/kg); drug related serious adverse event and dose limiting toxicity. These were evaluated at initial discharge from the NICU, and through short-term follow-up observations at 12 weeks and at 6 months. Results: Intracerebroventricular transplantation of ThWJ-MSCs via an anterior fontanelle tap to 9 newborn infants within the first 2 weeks after birth was well tolerated. None of patient showed any drug related serious adverse events or dose limiting toxicity related with ThWJ-MSCs. In one patient, CSF leakage occurred after a fontanelle tap but improved within a day without signs of infection. No infants expired in this phase 1 clinical trial. No dose-limiting toxicity was observed, as defined by death within 6hours after injection or anaphylactic shock following the injection.
Conclusion(s): Intracerebroventricular transplantation of allogeneic ThWJ-MSCs in the newborn infants including preterm infants was safe and feasible.
