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Neural stem cell transplantation could support neuronal replenishment and vascular reconstruction, but inconsistent in vivo fate, unclear mechanisms, and variable differentiation protocols limit translation. This study identifies a neural lineage-biased NSC optimized for neuronal and vascular recovery in the chronic phase after ischemic stroke.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/lineage-biased-neural-stem-cell-grafting-promotes-neuronal-differentiation-and-vascular-repair-in-the-chronic-phase-of-stroke/438964/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/lineage-biased-neural-stem-cell-grafting-promotes-neuronal-differentiation-and-vascular-repair-in-the-chronic-phase-of-stroke/438964.png","ImageObject",300,407,{"name":92,"@type":93},"Miles","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-09-30","2026-09-29",true,{"@type":102,"interactionType":103,"userInteractionCount":14},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What problem does this study address in ischemic stroke treatment?","Question",{"text":112,"@type":113},"Current therapies do not achieve effective functional neural and vascular restoration. The study targets limitations of NSC therapy such as inconsistent cell fate and unclear mechanisms.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How were the transplantable neural stem cells generated for comparison?",{"text":117,"@type":113},"Two derivation strategies were tested: one using embryoid body formation and another using a direct differentiation protocol that bypassed embryoid body formation.",{"name":119,"@type":110,"acceptedAnswer":120},"What were the main findings about nEB-NSCs after transplantation?",{"text":121,"@type":113},"nEB-NSCs showed higher neural stemness marker expression, improved neuronal differentiation with reduced astrocytic commitment, and faster neurovascular repair kinetics, supporting considerable motor recovery.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},438964,1790763490,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":14,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":139,"language":140,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":67,"update_tm":144,"read_time":36},13056703019404,"https://ap-avatar.wpscdn.com/davatar_29158cc5080c5b710cf443261637dec0","CNS Neuroscience & Therapeutics  \n| \u003Cbr> ORIGINAL ARTICLE  OPEN ACCESS \u003Cbr>Lineage-Biased Neural Stem Cell Grafting Promotes Neuronal Differentiation and Vascular Repair in the Chronic Phase of Stroke\u003Cbr>Tingting Zhang1,2,3  | Da Li1,2,3 | Qibiao Guan1,2,3 | Bin An1,2,4 | Yun Sun1,2,3 | Qiang Wang1,2,3 | Yukai Wang1,2,3,4  | Baoyang Hu1,2,3,4\u003Cbr>1State Key Laboratory of Organ Regeneration and Reconstruction, Institute of Zoology, Chinese Academy of Sciences, Beijing, China | 2Beijing Institute for Stem Cell and Regenerative Medicine, Beijing, China | 3University of Chinese Academy of Sciences, Beijing, China | 4National Stem Cell Resource Center, Chinese Academy of Sciences, Beijing, China\u003Cbr>Correspondence: Yukai Wang ([wangyukai@ioz.ac.cn](wangyukai@ioz.ac.cn)) | Baoyang Hu ([byhu@ioz.ac.cn](byhu@ioz.ac.cn))\u003Cbr>Received: 26 August 2025 | Revised: 10 November 2025 | Accepted: 18 November 2025\u003Cbr>Keywords: angiogenesis | cell replacement | cell therapy | chronic phase of ischemic stroke | embryonic body | neural stem cells | neurogenesis | vasculaturedevelopment |  |\n| --- | --- |\n| ABSTRACT\u003Cbr>Aims: Ischemic stroke (IS) is a harmful neurological disorder, yet current therapies fail to achieve effective functional neural and vascular restoration. Neural stem cell (NSC) transplantation offers high potential for neuronal replenishment and vascular reconstruction. However, its clinical application is limited by inconsistent in vivo cell fate, unclear therapeutic mechanisms, and variability in differentiation protocols. To address these limitations, we aimed to identify a neural lineage-biased NSC suitable for neuronal and vascular recovery after IS.\u003Cbr>Methods: We assessed two strategies for deriving transplantable NSCs: one involving embryoid body (EB) formation, and the other employing a direct differentiation protocol bypassing EB formation. We compared the cell fate of NSCs derived via both protocols in vitro and following transplantation into mice subjected to IS induced by transient middle cerebral artery occlusion (tMCAO) . RNA sequencing and immunofluorescence were used to assess cell fate. Cerebral blood flow (CBF) and behavioral tests were conducted to evaluate functional recovery.\u003Cbr>Results: Comparative analyses demonstrated that nEB-NSCs exhibit elevated neural stemness marker expression, improved neuronal differentiation with reduced astrocytic commitment, and accelerated neurovascular repair kinetics, contributing to considerable motor recovery.\u003Cbr>Conclusions: nEB-NSCs represent a promising cell source for enhancing neurovascular repair and functional recovery following IS. |  |\n| 1 | Introduction | disrupts neural circuitry, and compromises blood–brain barrier integrity [1] . During cerebral ischemia, the lack of oxygen and |\n| Accounting for approximately 85% of all stroke cases, isch- | nutrient delivery leads to the accumulation of reactive oxygen |\n| emic stroke (IS) is a severe cerebrovascular disorder that leads | species, resulting in neuronal death, brain–blood-barrier disrup- |\n| to widespread neuronal and vascular endothelial cell death, | tion, and neuroinflammation [2, 3] . As the condition progresses |\n| Tingting Zhang and Da Li contributed equally to this study. |  |\n| This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.\u003Cbr>© 2026 The Author(s). CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd. |  |\n\nCNS Neuroscience & Therapeutics, 2026; 32:e70701 1 of 16  \n[https://doi.org/10.1002/cns.70701](https://doi.org/10.1002/cns.70701)  \ninto the chronic phase, ongoing neuroinflammation and the formation of glial scars impede neuronal regeneration and neural circuit reconstruction, ultimately making motor function recovery more challenging [4, 5] .  \nNSCs can differentiate into neurons and release neurotrophic factors, facilitating neural repa","cbCaivVm3GxJoSSY","https://ap.wps.com/l/cbCaivVm3GxJoSSY","pdf",2818326,16,"English","# Abstract\n## Aims\n## Methods\n## Results\n## Conclusions\n# Introduction","[{\"question\":\"What problem does this study address in ischemic stroke treatment?\",\"answer\":\"Current therapies do not achieve effective functional neural and vascular restoration. The study targets limitations of NSC therapy such as inconsistent cell fate and unclear mechanisms.\"},{\"question\":\"How were the transplantable neural stem cells generated for comparison?\",\"answer\":\"Two derivation strategies were tested: one using embryoid body formation and another using a direct differentiation protocol that bypassed embryoid body formation.\"},{\"question\":\"What were the main findings about nEB-NSCs after transplantation?\",\"answer\":\"nEB-NSCs showed higher neural stemness marker expression, improved neuronal differentiation with reduced astrocytic commitment, and faster neurovascular repair kinetics, supporting considerable motor recovery.\"}]","Lineage-Biased Neural Stem Cell Grafting Promotes Neuronal Differentiation and Vascular Repair in the Chronic Phase of Stroke | PDF",1790687030]