Ogawa Yuko, Okinaka Yuka, Kikuchi-Taura Akie, Saino Orie, Tani-Yokoyama Ayumi, Masuda Satoru, Komatsu-Horii Miki, Ikemoto Yoshihiko, Kawamoto Atsuhiko, Fukushima Masanori, Taguchi Akihiko
Department of Regenerative Medicine Research, Foundation for Biomedical Research and Innovation at Kobe, Hyogo, Japan.
Translational Research Center for Medical Innovation, Foundation for Biomedical Research and Innovation at Kobe, Hyogo, Japan.
Front Med (Lausanne). 2022 Mar 11;9:681316. doi: 10.3389/fmed.2022.681316. eCollection 2022.
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 × 10 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.
本研究旨在评估将人外周血CD34阳性（CD34）细胞移植到小鼠慢性卒中模型中的安全性和有效性，以便在临床试验前获得临床前概念验证。在卒中诱导（慢性期）4周后，经静脉（iv）或经颈动脉（ia）移植粒细胞集落刺激因子（G-CSF）动员的人CD34细胞[50μl磷酸盐缓冲盐水（PBS）中含1×10个细胞]，并评估神经功能。在本研究中，使用严重联合免疫缺陷（SCID）小鼠以防止细胞治疗后出现过度免疫反应。细胞治疗后两周，与PBS对照组相比，ia CD34细胞组的神经功能有显著改善。治疗后8周仍维持治疗效果。即使单次给药，ia移植CD34细胞对慢性卒中也有显著治疗效果。基于这项临床前概念验证研究的结果，计划未来对慢性卒中患者进行自体外周血CD34细胞颈动脉内给药的临床试验。
