Human-Induced Pluripotent Stem Cell-Derived Neural Progenitor Cells Showed Neuronal Differentiation, Neurite Extension, and Formation of Synaptic Structures in Rodent Ischemic Stroke Brains.

Autor: Kanemura Y; Department of Biomedical Research and Innovation, Institute for Clinical Research, NHO Osaka National Hospital, Osaka 540-0006, Japan.; Department of Neurosurgery, NHO Osaka National Hospital, Osaka 540-0006, Japan., Yamamoto A; Department of Biomedical Research and Innovation, Institute for Clinical Research, NHO Osaka National Hospital, Osaka 540-0006, Japan., Katsuma A; Department of Biomedical Research and Innovation, Institute for Clinical Research, NHO Osaka National Hospital, Osaka 540-0006, Japan., Fukusumi H; Department of Biomedical Research and Innovation, Institute for Clinical Research, NHO Osaka National Hospital, Osaka 540-0006, Japan., Shofuda T; Department of Biomedical Research and Innovation, Institute for Clinical Research, NHO Osaka National Hospital, Osaka 540-0006, Japan., Kanematsu D; Department of Biomedical Research and Innovation, Institute for Clinical Research, NHO Osaka National Hospital, Osaka 540-0006, Japan., Handa Y; Department of Biomedical Research and Innovation, Institute for Clinical Research, NHO Osaka National Hospital, Osaka 540-0006, Japan., Sumida M; Department of Biomedical Research and Innovation, Institute for Clinical Research, NHO Osaka National Hospital, Osaka 540-0006, Japan., Yoshioka E; Department of Biomedical Research and Innovation, Institute for Clinical Research, NHO Osaka National Hospital, Osaka 540-0006, Japan., Mine Y; Department of Neurosurgery, NHO Tokyo Medical Center, Tokyo 152-8902, Japan.; Department of Physiology, Keio University School of Medicine, Tokyo 160-8582, Japan., Yamaguchi R; Department of Physiology, Keio University School of Medicine, Tokyo 160-8582, Japan.; Regenerative & Cellular Medicine Kobe Center, Sumitomo Pharma Co., Ltd., Kobe 650-0047, Japan., Okada M; Department of Brain Tumor Biology, Brain Research Institute, Niigata University, Niigata 951-8585, Japan.; Department of Neurosurgery, Brain Research Institute, Niigata University, Niigata 951-8585, Japan., Igarashi M; Department of Neurochemistry and Molecular Cell Biology, School of Medicine, Graduate School of Medical, Dental Sciences Niigata University, Niigata 951-8510, Japan., Sekino Y; Department of Veterinary Pathophysiology and Animal Health, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo 113-8657, Japan., Shirao T; AlzMed, Inc., Tokyo 113-8485, Japan., Nakamura M; Department of Orthopaedic Surgery, Keio University School of Medicine, Tokyo 160-8582, Japan., Okano H; Department of Physiology, Keio University School of Medicine, Tokyo 160-8582, Japan.; Keio Regenerative Medicine Research Center, Keio University, Kawasaki 210-0821, Japan.
Jazyk: angličtina
Zdroj: Cells [Cells] 2024 Apr 12; Vol. 13 (8). Date of Electronic Publication: 2024 Apr 12.
DOI: 10.3390/cells13080671
Abstrakt: Ischemic stroke is a major cerebrovascular disease with high morbidity and mortality rates; however, effective treatments for ischemic stroke-related neurological dysfunction have yet to be developed. In this study, we generated neural progenitor cells from human leukocyte antigen major loci gene-homozygous-induced pluripotent stem cells (hiPSC-NPCs) and evaluated their therapeutic effects against ischemic stroke. hiPSC-NPCs were intracerebrally transplanted into rat ischemic brains produced by transient middle cerebral artery occlusion at either the subacute or acute stage, and their in vivo survival, differentiation, and efficacy for functional improvement in neurological dysfunction were evaluated. hiPSC-NPCs were histologically identified in host brain tissues and showed neuronal differentiation into vGLUT-positive glutamatergic neurons, extended neurites into both the ipsilateral infarct and contralateral healthy hemispheres, and synaptic structures formed 12 weeks after both acute and subacute stage transplantation. They also improved neurological function when transplanted at the subacute stage with γ-secretase inhibitor pretreatment. However, their effects were modest and not significant and showed a possible risk of cells remaining in their undifferentiated and immature status in acute-stage transplantation. These results suggest that hiPSC-NPCs show cell replacement effects in ischemic stroke-damaged neural tissues, but their efficacy is insufficient for neurological functional improvement after acute or subacute transplantation. Further optimization of cell preparation methods and the timing of transplantation is required to balance the efficacy and safety of hiPSC-NPC transplantation.
Databáze: MEDLINE
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