Pre-Clinical Proof of Concept: Intra-Carotid Injection of Autologous CD34-Positive Cells for Chronic Ischemic Stroke

Abstract

This study was conducted to evaluate the safety and efficacy of human peripheral blood CD34 positive (CD34+) cells transplanted into a murine chronic stroke model to obtain pre-clinical proof of concept, prior to clinical testing. Granulocyte colony stimulating factor (G-CSF) mobilized human CD34+ cells [1 × 104 cells in 50 μl phosphate-buffered saline (PBS)] were intravenously (iv) or intra-carotid arterially (ia) transplanted 4 weeks after the induction of stroke (chronic stage), and neurological function was evaluated. In this study, severe combined immune deficiency (SCID) mice were used to prevent excessive immune response after cell therapy. Two weeks post cell therapy, the ia CD34+ cells group demonstrated a significant improvement in neurological functions compared to the PBS control. The therapeutic effect was maintained 8 weeks after the treatment. Even after a single administration, ia transplantation of CD34+ cells had a significant therapeutic effect on chronic stroke. Based on the result of this pre-clinical proof of concept study, a future clinical trial of autologous peripheral blood CD34+ cells administration in the intra-carotid artery for chronic stroke patients is planned.

CD34 positive cells as endothelial progenitor cells in biology and medicine

“…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 ).…”

Therapeutic Angiogenesis Using Autologous CD34-Positive Cells for Vascular Diseases

“…Ogawa et al 58) compared the therapeutic effect among iv injection of G-CSF-mobilized human CD34+ cells, intracarotid arterial (ia) injection of G-CSF-mobilized human CD34+ cells, and iv injection of PBS in SCID mice 4 weeks after permanent ligation of the MCA. At 8 weeks after injection, indicators of behavioral tests including CD34+ Cell Therapy wire hang test and rotarod test were significantly better in the ia injection group than in the iv injection group and the PBS group.…”