The safety and efficacy of umbilical cord blood mononuclear cells in individuals with spastic cerebral palsy: a randomized double-blind sham-controlled clinical trial

Abstract

Introduction The current multi-center, randomized, double-blind study was conducted among children with cerebral palsy (CP) to assess the safety and efficacy of umbilical cord blood mononuclear cell (UCB-MNC). We performed the diffusion tensor imaging to assess the changes in the white matter structure. Methods Males and females aged 4 to 14 years old with spastic CP were included. Eligible participants were allocated in 4:1 ratio to be in the experimental or control groups; respectively. Individuals who were assigned in UCB-MNC group were tested for human leukocyte antigen (HLA) and fully-matched individuals were treated with UCB-MNCs. A single dose (5 × 106 /kg) UCB-MNCs were administered via intrathecal route in experimental group. The changes in gross motor function measure (GMFM)-66 from baseline to one year after treatment were the primary endpoints. The mean changes in modified Ashworth scale (MAS), pediatric evaluation of disability inventory (PEDI), and CP quality of life (CP-QoL) were also evaluated and compared between groups. The mean changes in fractional anisotropy (FA) and mean diffusivity (MD) of corticospinal tract (CST) and posterior thalamic radiation (PTR) were the secondary endpoints. Adverse events were safety endpoint. Results There were 72 included individuals (36 cases in each group). The mean GMFM-66 scores increased in experimental group; compared to baseline (+ 9.62; 95%CI: 6.75, 12.49) and control arm (β: 7.10; 95%CI: 2.08, 12.76; Cohen’s d: 0.62) and mean MAS reduced in individuals treated with UCB-MNCs compared to the baseline (-0.87; 95%CI: -1.2, -0.54) and control group (β: -0.58; 95%CI: -1.18, -0.11; Cohen’s d: 0.36). The mean PEDI scores and mean CP-QoL scores in two domains were higher in the experimental group compared to the control. The imaging data indicated that mean FA increased and MD decreased in participants of UCB-MNC group indicating improvements in white matter structure. Lower back pain, headaches, and irritability were the most common adverse events within 24 h of treatment that were related to lumbar puncture. No side effects were observed during follow-up. Conclusions This trial showed that intrathecal injection of UCB-MNCs were safe and effective in children with CP. Trial Registration The study was registered with ClinicalTrials.gov (NCT03795974).

Clinical results of neurorestorative cell therapies and therapeutic indications according to cellular bio-proprieties

“…Human umbilical cord blood-MSC infusion with basic rehabilitation was safe and effective in improving gross motor and comprehensive functions in children with CP [ 87 ]. The scores of activities of daily living (ADL), comprehensive function assessment (CFA), and gross motor function measure (GMFM) scales were differences between the human umbilical cord-MSC group and the control group [ 88 ]. Intrathecal transplantation of umbilical cord blood MNCs in 36 individuals with spastic CP showed score improvements in modified Ashworth scale (MAS), pediatric evaluation of disability inventory (PEDI), and CP quality of life (CP-QoL) compared to the control [ 89 ] (Note: In another article with same registered No.…”

Effects of human umbilical cord blood mononuclear cells on ovalbumin-induced asthma in mice

“…Compared with MNCs obtained from adult bone marrow MNCs (BMMNCs), umbilical cord blood MNCs (UCMNCs) have higher cell viability and lower reaction to cytotoxic T cells and T-helper (Th)1 cells ( 5 ). The therapeutic potential of UCMNCs has been reported in many animal models involving bronchopulmonary dysplasia ( 6 ), neonatal lung injury ( 7 ), and acute myocardial infarction ( 8 ), and in some clinical studies for diseases such as multiple system atrophy ( 9 ) and spastic cerebral palsy ( 10 ). The non-invasiveness, high accessibility, and few ethical constraints of UCMNCs make them a suitable alternative to BMMNCs.…”