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

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) administ...

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Autores principales: Amirbekyan, Mari, Cheng, Jeffrey P., Adhikarla, Vikram, Moschonas, Eleni H., Bondi, Corina O., Rockne, Russell C., Kline, Anthony E., Gutova, Margarita
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Journal Experts 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10503851/
https://www.ncbi.nlm.nih.gov/pubmed/37720043
http://dx.doi.org/10.21203/rs.3.rs-3242570/v1
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author Amirbekyan, Mari
Cheng, Jeffrey P.
Adhikarla, Vikram
Moschonas, Eleni H.
Bondi, Corina O.
Rockne, Russell C.
Kline, Anthony E.
Gutova, Margarita
author_facet Amirbekyan, Mari
Cheng, Jeffrey P.
Adhikarla, Vikram
Moschonas, Eleni H.
Bondi, Corina O.
Rockne, Russell C.
Kline, Anthony E.
Gutova, Margarita
author_sort Amirbekyan, Mari
collection PubMed
description 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, immunocompetent adult female rats received a controlled cortical impact injury (CCI) or sham surgery. LMNSC008 cells or a vehicle (VEH) 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. The data demonstrate a robust proof-of-concept for LMNSC008 therapy for TBI and provides a strong rationale for IN delivery for translation in TBI patients.
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spelling pubmed-105038512023-09-16 Neuroprotective potential of intranasally delivered L-myc immortalized human neural stem cells in female rats after a controlled cortical impact injury Amirbekyan, Mari Cheng, Jeffrey P. Adhikarla, Vikram Moschonas, Eleni H. Bondi, Corina O. Rockne, Russell C. Kline, Anthony E. Gutova, Margarita Res Sq Article 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, immunocompetent adult female rats received a controlled cortical impact injury (CCI) or sham surgery. LMNSC008 cells or a vehicle (VEH) 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. The data demonstrate a robust proof-of-concept for LMNSC008 therapy for TBI and provides a strong rationale for IN delivery for translation in TBI patients. American Journal Experts 2023-09-05 /pmc/articles/PMC10503851/ /pubmed/37720043 http://dx.doi.org/10.21203/rs.3.rs-3242570/v1 Text en https://creativecommons.org/licenses/by/4.0/This work is licensed under a Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/) , which allows reusers to distribute, remix, adapt, and build upon the material in any medium or format, so long as attribution is given to the creator. The license allows for commercial use.
spellingShingle Article
Amirbekyan, Mari
Cheng, Jeffrey P.
Adhikarla, Vikram
Moschonas, Eleni H.
Bondi, Corina O.
Rockne, Russell C.
Kline, Anthony E.
Gutova, Margarita
Neuroprotective potential of intranasally delivered L-myc immortalized human neural stem cells in female rats after a controlled cortical impact injury
title Neuroprotective potential of intranasally delivered L-myc immortalized human neural stem cells in female rats after a controlled cortical impact injury
title_full Neuroprotective potential of intranasally delivered L-myc immortalized human neural stem cells in female rats after a controlled cortical impact injury
title_fullStr Neuroprotective potential of intranasally delivered L-myc immortalized human neural stem cells in female rats after a controlled cortical impact injury
title_full_unstemmed Neuroprotective potential of intranasally delivered L-myc immortalized human neural stem cells in female rats after a controlled cortical impact injury
title_short Neuroprotective potential of intranasally delivered L-myc immortalized human neural stem cells in female rats after a controlled cortical impact injury
title_sort neuroprotective potential of intranasally delivered l-myc immortalized human neural stem cells in female rats after a controlled cortical impact injury
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10503851/
https://www.ncbi.nlm.nih.gov/pubmed/37720043
http://dx.doi.org/10.21203/rs.3.rs-3242570/v1
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