Efficacy and safety of allogeneic umbilical cord blood mononuclear cells therapy in children with autism spectrum disorder and immune dysregulation: a single-center, double-blinded, randomized, placebo-controlled trial

Immune-inflammatory dysregulation is increasingly implicated in the pathogenesis of autism spectrum disorder (ASD). Umbilical cord blood mononuclear cells (UCB-MNCs), with their immunomodulatory effects, represent a promising therapeutic avenue by potentially alleviating neuroinflammation. This study aimed to evaluate the safety and efficacy of multiple intravenous infusions of allogeneic UCB-MNCs in children with ASD and peripheral immune dysregulation. In this single-center, double-blind, randomized, placebo-controlled trial (RCT), 34 children (aged 3 to 8 years) diagnosed with ASD were randomly assigned to receive intravenous infusion of allogeneic UCB-MNCs (3 × 10⁸ cells per infusion) ( n = 17) or placebo ( n = 17) four times with 1-week interval, alongside their existing rehabilitation therapy, and followed up for 13 weeks. The primary endpoint were the Total score of the Social Responsiveness Scale-2 (SRS-2). Additional endpoints was changes of the five domains of the SRS-2, the Vineland Adaptive Behavior Scales-3 (Vineland-3), the Childhood Autism Rating Scale (CARS), Aberrant Behavior Checklist (ABC), Swanson, Nolan, and Pelham Rating Scale-IV (SNAP-IV), Self-Rating Anxiety Scale (SAS) and safety. At final follow-up, the UCB-MNCs group demonstrated a significantly greater reduction in the SRS-2 Total scores (LS Mean Difference = − 6.03, 95% confidence interval [CI]: − 11.93 to − 0.14, P = 0.045) and Social Cognition domain (LS Mean Difference = − 9.95, 95% confidence interval [CI]: − 15.90 to − 4.00, P = 0.002) scores compared to the placebo group. No major allogeneic UCB-MNCs transplantation-related adverse events occurred. Allogeneic UCB-MNCs transplantation demonstrated preliminary safety and potential efficacy in improving specific aspects of symptoms in children with ASD and peripheral immune dysregulation. Trial registration This study was registered on ChiCTR.org.cn (Identifier: ChiCTR2400082762). Date registered 12 April 2024. https://www.chictr.org.cn/index.html .