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Article: Transplanting Human Neural Stem Cells with ≈50% Reduction of SOX9 Gene Dosage Promotes Tissue Repair and Functional Recovery from Severe Spinal Cord Injury

TitleTransplanting Human Neural Stem Cells with ≈50% Reduction of SOX9 Gene Dosage Promotes Tissue Repair and Functional Recovery from Severe Spinal Cord Injury
Authors
Keywordshuman neural stem cells
motor neurons
pluripotent stem cells
SOX9
spinal cord injury
Issue Date9-Jun-2023
PublisherWiley Open Access
Citation
Advanced Science, 2023 How to Cite?
Abstract

Neural stem cells (NSCs) derived from human pluripotent stem cells (hPSCs) are considered a major cell source for reconstructing damaged neural circuitry and enabling axonal regeneration. However, the microenvironment at the site of spinal cord injury (SCI) and inadequate intrinsic factors limit the therapeutic potential of transplanted NSCs. Here, it is shown that half dose of SOX9 in hPSCs-derived NSCs (hNSCs) results in robust neuronal differentiation bias toward motor neuron lineage. The enhanced neurogenic potency is partly attributed to the reduction of glycolysis. These neurogenic and metabolic properties retain after transplantation of hNSCs with reduced SOX9 expression in a contusive SCI rat model without the need for growth factor-enriched matrices. Importantly, the grafts exhibit excellent integration properties, predominantly differentiate into motor neurons, reduce glial scar matrix accumulation to facilitate long-distance axon growth and neuronal connectivity with the host as well as dramatically improve locomotor and somatosensory function in recipient animals. These results demonstrate that hNSCs with half SOX9 gene dosage can overcome extrinsic and intrinsic barriers, representing a powerful therapeutic potential for transplantation treatments for SCI.


Persistent Identifierhttp://hdl.handle.net/10722/329181
ISSN
2023 Impact Factor: 14.3
2023 SCImago Journal Rankings: 3.914
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorLiu, JA-
dc.contributor.authorTam, KW-
dc.contributor.authorChen, YL-
dc.contributor.authorFeng, XL-
dc.contributor.authorChan, CWL-
dc.contributor.authorLo, ALH-
dc.contributor.authorWu, KLK-
dc.contributor.authorHui, MN-
dc.contributor.authorWu, MH-
dc.contributor.authorChan, KKK-
dc.contributor.authorCheung, MPL-
dc.contributor.authorCheung, CW-
dc.contributor.authorShum, DKY-
dc.contributor.authorChan, YS-
dc.contributor.authorCheung, M-
dc.date.accessioned2023-08-05T07:55:54Z-
dc.date.available2023-08-05T07:55:54Z-
dc.date.issued2023-06-09-
dc.identifier.citationAdvanced Science, 2023-
dc.identifier.issn2198-3844-
dc.identifier.urihttp://hdl.handle.net/10722/329181-
dc.description.abstract<p>Neural stem cells (NSCs) derived from human pluripotent stem cells (hPSCs) are considered a major cell source for reconstructing damaged neural circuitry and enabling axonal regeneration. However, the microenvironment at the site of spinal cord injury (SCI) and inadequate intrinsic factors limit the therapeutic potential of transplanted NSCs. Here, it is shown that half dose of <em>SOX9</em> in hPSCs-derived NSCs (hNSCs) results in robust neuronal differentiation bias toward motor neuron lineage. The enhanced neurogenic potency is partly attributed to the reduction of glycolysis. These neurogenic and metabolic properties retain after transplantation of hNSCs with reduced <em>SOX9</em> expression in a contusive SCI rat model without the need for growth factor-enriched matrices. Importantly, the grafts exhibit excellent integration properties, predominantly differentiate into motor neurons, reduce glial scar matrix accumulation to facilitate long-distance axon growth and neuronal connectivity with the host as well as dramatically improve locomotor and somatosensory function in recipient animals. These results demonstrate that hNSCs with half <em>SOX9</em> gene dosage can overcome extrinsic and intrinsic barriers, representing a powerful therapeutic potential for transplantation treatments for SCI.<br></p>-
dc.languageeng-
dc.publisherWiley Open Access-
dc.relation.ispartofAdvanced Science-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.subjecthuman neural stem cells-
dc.subjectmotor neurons-
dc.subjectpluripotent stem cells-
dc.subjectSOX9-
dc.subjectspinal cord injury-
dc.titleTransplanting Human Neural Stem Cells with ≈50% Reduction of SOX9 Gene Dosage Promotes Tissue Repair and Functional Recovery from Severe Spinal Cord Injury-
dc.typeArticle-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1002/advs.202205804-
dc.identifier.scopuseid_2-s2.0-85161320705-
dc.identifier.eissn2198-3844-
dc.identifier.isiWOS:001003351200001-
dc.identifier.issnl2198-3844-

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