Umbilical cord blood CD34+ cells administration improved neurobehavioral status and alleviated brain injury in a mouse model of cerebral palsy

Abstract

Purpose Cerebral palsy (CP) is the most common neuromuscular disease in children, and currently, there is no cure. Several studies have reported the benefits of umbilical cord blood (UCB) cell treatment for CP. However, these studies either examined the effects of UCB cell fraction with a short experimental period or used neonatal rat models for a long-term study which displayed an insufficient immunological reaction and clearance of human stem cells. Here, we developed a CP model by hypoxia-ischemic injury (HI) using immunodeficient mice and examined the effects of human UCB CD34+ hematopoietic stem cells (HSCs) on CP therapy over a period of 8 weeks. Methods Sixty postnatal day-9 (P9) mouse pups were randomly divided into 4 groups (n = 15/group) as follows: (1) sham operation (control group), (2) HI-induced CP model, (3) CP model with CD34+ HSC transplantation, and (4) CP model with CD34- cell transplantation. Eight weeks after insult, the sensorimotor performance was analyzed by rotarod treadmill, gait dynamic, and open field assays. The pathological changes in brain tissue of mice were determined by HE staining, Nissl staining, and MBP immunohistochemistry of the hippocampus in the mice. Results HI brain injury in mice pups resulted in significant behavioral deficits and loss of neurons. Both CD34+ HSCs and CD34- cells improved the neurobehavioral statuses and alleviated the pathological brain injury. In comparison with CD34- cells, the CD34+ HSC compartments were more effective. Conclusion These findings indicate that CD34+ HSC transplantation was neuroprotective in neonatal mice and could be an effective therapy for CP.

Underlying causes of cerebral palsy: public health perspectives

“…Intracerebrally transplanted CD34 + haematopoietic stem cells effectively improved sensorimotor performances in hypoxia-ischaemic injury-induced mice. Notably, the treatment also considerably improved hypoxia-ischaemic injury-induced exploratory behaviours and locomotion impairments [7].…”

Umbilical Cord Blood-Derived Cell Therapy for Perinatal Brain Injury: A Systematic Review & Meta-Analysis of Preclinical Studies

“…The current literature is also suggestive that UCB-derived cell therapy is effective in the treatment of perinatal brain injury in both small and large animal models. Chang et al, (2021) assessed the efficacy of human UCB-derived CD34+ cells on a mouse model of HIE and showed that these cells were effective in reducing neuronal loss and improving motor function [31]. The neuroprotective effects of UCB-derived cells have also been shown to be effective in larger animal models, with cord blood mononuclear cells being associated with significantly reduced neuronal apoptosis, astrogliosis and inflammation in lamb models of perinatal asphyxia [28].…”

CD34 positive cells as endothelial progenitor cells in biology and medicine

“…Supportively, Tsuji and colleagues reported that CB-CD34 + cells increased blood stream to the ischemic zone and decreased missing of ipsilateral hemisphere volume in a neonatal stroke model ( Tsuji et al, 2014 ). Also, CB-CD34 + cells alleviates pathological brain injury and improves the neurobehavioral status in a cerebral palsy model ( Chang et al, 2021 ). More recently, Ogawa et al illustrated that transplantation of PB-CD34 + cells improved neurological functions, including grip strength test (to evaluate neuromuscular function), the water maze assay (to evaluate the spatial education skill), and the rotarod test (to evaluate sensorimotor skills) in a murine SCID chronic stroke model, providing another preclinical proof of the CD34 + therapy concept in ischemic strokes ( Ogawa et al, 2022 ).…”