Abstract
Neonatal hypoxic-ischemic encephalopathy (HIE) in preterm infants lacks effective treatment and remains a leading cause of long-term neurological impairment. Autologous umbilical cord blood (UCB)-derived CD34⁺ cell therapy shows therapeutic potential; however, limited UCB volume in preterm infants often yields insufficient cells for clinical use. Recent advances in ex vivo expansion using chemically defined, albumin- and cytokine-free systems enable efficient proliferation of CD34⁺ hematopoietic stem cells. We evaluated the safety and efficacy of intravenously administered, ex vivo expanded CD34⁺ cells derived from human UCB in a mouse model of preterm HIE. Human UCB-derived CD34⁺ cells were cultured for 10 days using a chemically defined, serum- and cytokine-free expansion protocol. Mice with unilateral hypoxic-ischemic injury on postnatal day 5 received expanded or unexpanded CD34⁺ cells (1 × 10⁵ cells per animal) 48 h after injury. Expanded CD34⁺ cells were well tolerated and improved sensorimotor asymmetry, as assessed by the cylinder test, and reduced astrocyte and microglial activation in the injured brain compared with untreated HIE mice. Therapeutic effects did not significantly differ between expanded and unexpanded CD34⁺ cells. Ex vivo expansion under chemically defined conditions may enable autologous CD34⁺ cell therapy for preterm infants with limited UCB volume and represents a promising approach for regenerative treatment of neonatal brain injury.
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Data availability
The data that support the findings of this study are available from the corresponding author upon reasonable request. Due to confidentiality agreements, some information related to the cell materials provided by Celaid Therapeutics is not publicly available.
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We gratefully acknowledge the support of Celaid Therapeutics, who provided both the cell materials and funding for this research.
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This study was financially supported by Celaid Therapeutics, which also provided the cells used in the experiments. The funder had no influence on the study design, data collection and analysis, decision to publish, or manuscript preparation. Additional support was provided by JSPS KAKENHI (Grant Number JP222640019).
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Natsumu Arai: Collection and/or assembly of data (behavioral tests, etc.), data analysis and interpretation, figure preparation, manuscript writing. Emi Tanaka: Collection and/or assembly of data (animal model and behavioral tests, etc.), data analysis and interpretation, study design, critical manuscript review. Satoshi Ohnishi: Project supervision, critical revision of the manuscript for important intellectual content. Takashi Hamazaki: Project supervision, critical revision of the manuscript for important intellectual content. All authors approved the final manuscript.
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This study was financially supported by Celaid Therapeutics, which also provided the cells used in the experiments. The funder had no influence on the study design, data collection and analysis, decision to publish, or manuscript preparation. Additional support was provided by JSPS KAKENHI (Grant Number JP222640019).
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Arai, N., Tanaka, E., Ohnishi, S. et al. Intravenous administration of ex vivo expanded human umbilical cord blood-derived CD34⁺ cells in a preterm hypoxic-ischemic encephalopathy mouse model. Sci Rep (2026). https://doi.org/10.1038/s41598-026-48204-z
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DOI: https://doi.org/10.1038/s41598-026-48204-z