ORIGINAL RESEARCH article
Front. Immunol.
Sec. Multiple Sclerosis and Neuroimmunology
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1650092
This article is part of the Research TopicNeuroinflammation, Neurodegeneration, and Auditory-Vestibular DisordersView all 20 articles
Human pluripotent stem cell-derived neuronal progenitor cells improve motor function and promote neurogenesis in a stroke model
Provisionally accepted
Hyun Jin Kim1
Dong Hee Kim1Jee In Choi1
Hye Ryeong Sim1
Sangyong Jung1Dong-Youn Hwang1*
MinYoung Kim1,2*- 1CHA University School of Medicine, Pocheon-si, Republic of Korea
- 2CHA University Bundang Medical Center, Seongnam-si, Republic of Korea
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Introduction: Stroke remains a leading cause of long-term disability worldwide. The limited therapeutic window of current treatments underscores the need for alternative regenerative strategies. Neural progenitor cells (NPCs) are promising candidates for brain repair. However, the optimal timing of therapy and the mechanisms underlying its effects on ischemic stroke remain unclear. Methods: To evaluate their efficacy, NPCs were administered intravenously to a subacute stroke (day 7) rat model. The outcomes were determined by comparison with saline treatment using neurobehavioral assessments, infarct volume measurements, and molecular assays. In addition, NPC secretome profiling was performed to assess the underlying cellular mechanisms. Results: The NPC group showed significant improvement in motor function at 3 weeks post-injection (p<0.001) and reduced infarct volume (p<0.05). Immunofluorescence analysis revealed increased BrdU/DCX colocalization in the subventricular zone on day 14 (p<0.05). Western blotting confirmed the upregulation of NeuN (p<0.01), Nestin (p<0.05), and DCX (p=0.0668) in the ipsilesional brain on day 28. The neuroprotection-related pathways revealed elevated protein levels of phosphorylated Akt, GSK3β, Erk, and CREB (p<0.05). Secretome profiling of NPC-conditioned medium and extracellular vesicles identified key regenerative factors such as Angiopoietin-1, BDNF, bFGF, MMP2, EGF, and VEGFa. This is a provisional file, not the final typeset article Discussion: NPC administration during the subacute phase of stroke promoted functional recovery by promoting neurogenesis and modulating key survival pathways. These results highlight the therapeutic potential of NPCs as cell-based interventions for delayed stroke treatment and provide mechanistic insights into their reparative effects.
Keywords: cell therapy, paracrine, neurorestoration, Neurogenesis, neuroplasticity
Received: 19 Jun 2025; Accepted: 29 Aug 2025.
Copyright: © 2025 Kim, Kim, Choi, Sim, Jung, Hwang and Kim. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Dong-Youn Hwang, CHA University School of Medicine, Pocheon-si, Republic of Korea
MinYoung Kim, CHA University School of Medicine, Pocheon-si, Republic of Korea
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