Umbilical cord blood cell clearance post-infusion in immune competent children with cerebral palsy

Abstract

Umbilical cord blood cells have therapeutic potential for neurological disorders, through a paracrine mechanism of action. A greater understanding of the safety and immunological effects of allogeneic donor cord blood cells in the context of a healthy recipient immune system, such as in cerebral palsy, is needed. This study aimed to determine how quickly donor cord blood cells were cleared from the circulation in children with cerebral palsy who received a single intravenous infusion of 12/12 human leucocyte antigen (HLA) matched sibling cord blood cells. Twelve participants with cerebral palsy aged 2-12 years received cord blood cell infusions as part of a phase I trial of umbilical blood infusion for cerebral palsy. Digital droplet PCR analysis of DNA copy number variants specific to donor and recipient was used to assess donor DNA clearance at five timepoints post infusion, a surrogate measure of cell clearance. Donor cells were cleared from 3 months post-infusion in 11/12 participants. When detected, donor DNA was at a fraction of 0.01 - 0.31% of total DNA with no signs of graft-versus-host disease (GvHD) in any participant. The donor DNA clearance times provided by this study have important implications for understanding safety of allogeneic cord blood cell infusion for cerebral palsy and translational tissue engineering or regenerative medicine research in other disorders.