ORIGINAL RESEARCH article
Front. Cell. Neurosci.
Sec. Cellular Neuropathology
This article is part of the Research TopicNeural Differentiation and Neurorestorative Effects of Mesenchymal Stem Cells in Brain DisordersView all articles
Adipose-Derived Stem Cells-Conditioned Medium Mitigate Ischemia-Induced Neuronal Injury via JAK1/STAT3 Signaling Pathway
Provisionally accepted
- 1Department of Neurology, Fujian Medical University Union Hospital, Fuzhou, Fujian Province, China
- 2Department of Geriatric Medicine, Fuzhou University Affiliated Provincial Hospital, Fuzhou, China
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Abstract Introduction: Adipose-derived stem cells (ADSCs) demonstrate therapeutic potential for ischemic stroke, primarily through paracrine actions. However, the specific intracellular signaling pathways underlying these benefits remain unclear. This study investigates the critical role of JAK1/STAT3 signaling in neuroprotection mediated by ADSC-conditioned medium (ADSC-CM). Methods: We employed a dual-model approach. In vivo, rats subjected to transient middle cerebral artery occlusion (tMCAO) received intravenous ADSC-CM or vehicle at 2, 24, and 48 hours post-ischemia, with or without the JAK1 inhibitor GLPG0634. Neurological function was evaluated over a period of 7 days. Subsequently, infarct volume, brain edema, neuronal survival, neurovascular regeneration, synaptic ultrastructure, mitochondrial function, and energy metabolism were analyzed. In vitro, primary cortical neurons subjected to oxygen-glucose deprivation (OGD) were treated with ADSC-CM with or without GLPG0634 to assess neurite outgrowth. Activation of the JAK1/STAT3 pathway was confirmed by Western blot in both models. This is a provisional file, not the final typeset article Results: In vivo, ADSC-CM significantly improved neurological function, reduced infarct volume and brain edema, and enhanced neuronal survival, nerve fiber regeneration, angiogenesis, synaptic plasticity, and mitochondrial function in tMCAO rats. In vitro, ADSC-CM promoted neurite outgrowth in OGD-injured neurons. Crucially, all these multifaceted neuroprotective effects were completely abolished by co-treatment with GLPG0634. Mechanistically, ADSC-CM robustly activated JAK1 and STAT3 phosphorylation in both models, an effect effectively inhibited by GLPG0634. Discussion: The neuroprotective effects of ADSC-CM are mechanistically linked to the activation of the JAK1/STAT3 pathway, which mitigates ischemic damage by promoting neuronal salvage, neurovascular regeneration, synaptic plasticity, and metabolic recovery, thereby enhancing neurological functional recovery after stroke.
Keywords: adipose-derived stem cells, conditioned medium, Ischemicstroke, JAK1/STAT3 signaling, mitochondrialfunction, Neurovascular Regeneration, Paracrine effect, synaptic plasticity
Received: 12 Nov 2025; Accepted: 06 Feb 2026.
Copyright: © 2026 Huang, Zheng, Lai, Zhang, Chen and Liu. 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: Nan Liu
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