Background Concomitant administration of allogeneic umbilical cord blood (UCB) infusion and erythropoietin (EPO) showed therapeutic efficacy in children with cerebral palsy (CP). However, no clinical studies have investigated the effects of UCB and EPO combination therapy using a 2 × 2 four-arm factorial blinded design with four arms. This randomized placebo-controlled trial aimed to identify the synergistic and individual efficacies of UCB cell and EPO for the treatment of CP. Methods Children diagnosed with CP were randomly segregated into four groups: (A) UCB+EPO, (B) UCB+placebo EPO, (C) placebo UCB+EPO, and (D) placebo UCB+placebo EPO. Based on the UCB unit selection criteria of matching for ≥ 4/6 of human leukocyte antigen (HLA)-A, -B, and DRB1 and total nucleated cell (TNC) number of ≥ 3 × 107/kg, allogeneic UCB was intravenously infused and 500 IU/kg human recombinant EPO was administered six times. Functional measurements, brain imaging studies, and electroencephalography were performed from baseline until 12 months post-treatment. Furthermore, adverse events were closely monitored. Results Eighty-eight of 92 children enrolled (3.05 ± 1.22 years) completed the study. Change in gross motor performance measure (GMPM) was greater in group A than in group D at 1 month (△2.30 vs. △0.71, P = 0.025) and 12 months (△6.85 vs. △2.34, P = 0.018) post-treatment. GMPM change ratios were calculated to adjust motor function at the baseline. Group A showed a larger improvement in the GMPM change ratio at 1 month and 12 months post-treatment than group D. At 12 months post-treatment, the GMPM change ratios were in the order of groups A, B, C, and D. These results indicate synergistic effect of UCB and EPO combination better than each single therapy. In diffusion tensor imaging, the change ratio of fractional anisotropy at spinothalamic radiation was higher in group A than group D in subgroup of age ≥ 3 years. Additionally, higher TNC and more HLA-matched UCB units led to better gross motor outcomes in group A. Adverse events remained unchanged upon UCB or EPO administration. Conclusions These results indicate that the efficacy of allogeneic UCB cell could be potentiated by EPO for neurological recovery in children with CP without harmful effects. Trial registration ClinicalTrials.gov, NCT01991145, registered 25 November 2013.

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To assess whether functional (electrophysiological) parameters are related to changes in the structural (microvascular) parameters in diabetic retina. Methods: This prospective cohort study included 380 eyes of patients with diabetes mellitus (DM) and 160 eyes of healthy controls. We analysed the electroretinogram (ERG) parameters and vascular parameters acquired from optical coherence tomography (OCT) angiography according to the diabetic retinopathy (DR) severity from early to late stages of DR. Results: After exclusion, 366 eyes of diabetes and 157 eyes of controls were included in the analysis. The mean age at enrolment was 65.4 AE 7.8 years, and 177 (33.84%) were male. The amplitude and implicit time of the rod and cone and combined response ERG b-wave were significantly reduced and prolonged in the eyes of patients with DM, compared to the controls. There was a positive correlation between the amplitude and vessel density (VD) of the superficial plexus and a negative correlation between the implicit time and superficial VD in the scotopic and combined response b-wave. Interestingly, there was no correlation between electrophysiological parameters and deep VD. These correlations between electrophysiological parameters and vascular parameters were not significant in the non-diabetic, healthy control group. Conclusions: Functional and structural impairments precede the clinical manifestation of DR. We also found that these neural impairments, evaluated by ERG, were correlated with superficial VD. However, this correlation was absent in the healthy and early DR groups. These findings carefully suggest that neuronal dysfunction is linked to vascular dysfunction in type 2 diabetes.