Motor Function and Safety after Allogeneic Cord Blood and Cord Tissue-Derived Mesenchymal Stromal Cells in Cerebral Palsy: an Open-Label, Randomized Trial.

Aim To evaluate safety and motor function after treatment with allogeneic umbilical cord blood (AlloCB) or umbilical cord tissue-derived mesenchymal stromal cells (hCT-MSC) in children with cerebral palsy (CP). Method Ninety-one children (52 males, 39 females; median age 3 years 7 months [range 2-5 years]) with CP due to hypoxic-ischemic encephalopathy, stroke, or periventricular leukomalacia were randomized to three arms: (1) the AlloCB group received 10 x 10(7) AlloCB total nucleated cells (TNC) per kilogram at baseline (n = 31); (2) the hCT-MSC group received 2 x 10(6) hCT-MSC at baseline, 3 months, and 6 months (n = 28); (3) the natural history control group received 10 x 10(7) AlloCB TNC per kilogram at 12 months (n = 31). Motor function was assessed with the Gross Motor Function Measure-66 (GMFM-66) and Peabody Developmental Motor Scale, Second Edition. Results Infusions (n = 143) were well tolerated, with eight infusion reactions (three in the AlloCB group, five in hCT-MSC) and no other safety concerns. At 12 months, the mean differences (95% confidence intervals [CI]) between actual and expected changes in GMFM-66 score were AlloCB 5.8 points (3.4-8.2), hCT-MSC 4.3 (2.2-6.4), and natural history 3.1 (1.4-5.0). In exploratory, post hoc analysis, the mean GMFM-66 score (95% CI) of the hCT-MSC group was 1.4 points higher than natural history (-1.1 to 4.0; p = 0.27), and the AlloCB group was 3.3 points higher than natural history (0.59-5.93; p = 0.02) after adjustment for baseline Gross Motor Function Classification System level, GMFM-66 score, and etiology. Interpretation High-dose AlloCB is a potential cell therapy for CP and should be further tested in a randomized, blinded, placebo-controlled trial.