Neuroprotective potential of intranasally delivered L-myc immortalized human neural stem cells in female rats after a controlled cortical impact injury.

Publisher: Nature Publishing Group Country of Publication: England NLM ID: 101563288 Publication Model: Electronic Cited Medium: Internet ISSN: 2045-2322 (Electronic) Linking ISSN: 20452322 NLM ISO Abbreviation: Sci Rep Subsets: MEDLINE

Original Publication: London : Nature Publishing Group, copyright 2011-

Brain Injuries, Traumatic*/metabolism ; Neural Stem Cells*/metabolism ; White Matter*/metabolism; Rats ; Humans ; Animals ; Female ; Neuroprotection ; Brain/metabolism ; Disease Models, Animal

Efficacious stem cell-based therapies for traumatic brain injury (TBI) depend on successful delivery, migration, and engraftment of stem cells to induce neuroprotection. L-myc expressing human neural stem cells (LMNSC008) demonstrate an inherent tropism to injury sites after intranasal (IN) administration. We hypothesize that IN delivered LMNSC008 cells migrate to primary and secondary injury sites and modulate biomarkers associated with neuroprotection and tissue regeneration. To test this hypothesis, immunocompetent adult female rats received either controlled cortical impact injury or sham surgery. LMNSC008 cells or a vehicle were administered IN on postoperative days 7, 9, 11, 13, 15, and 17. The distribution and migration of eGFP-expressing LMNSC008 cells were quantified over 1 mm-thick optically cleared (CLARITY) coronal brain sections from TBI and SHAM controls. NSC migration was observed along white matter tracts projecting toward the hippocampus and regions of TBI. ELISA and Nanostring assays revealed a shift in tissue gene expression in LMNSC008 treated rats relative to controls. LMNSC008 treatment reduced expression of genes and pathways involved in inflammatory response, microglial function, and various cytokines and receptors. Our proof-of-concept studies, although preliminary, support the rationale of using intranasal delivery of LMNSC008 cells for functional studies in preclinical models of TBI and provide support for potential translatability in TBI patients.
(© 2023. Springer Nature Limited.)

Update of: Res Sq. 2023 Sep 05:rs.3.rs-3242570. doi: 10.21203/rs.3.rs-3242570/v1. (PMID: 37720043)

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R56 NS113810 United States NS NINDS NIH HHS; T32 NS007433 United States NS NINDS NIH HHS; R01 NS084967 United States NS NINDS NIH HHS; R21 NS099683 United States NS NINDS NIH HHS; R01 HD069620 United States HD NICHD NIH HHS; R01 NS121037 United States NS NINDS NIH HHS; R01 NS110609 United States NS NINDS NIH HHS; P30 CA033572 United States CA NCI NIH HHS; R21 NS099674 United States NS NINDS NIH HHS; R03 NS094950 United States NS NINDS NIH HHS

Date Created: 20231019 Date Completed: 20231023 Latest Revision: 20241216

20250114

PMC10587115

10.1038/s41598-023-44426-7

37857701