The Route by Which Intranasally Delivered Stem Cells Enter the Central Nervous System

Intranasal administration is a promising route of delivery of stem cells to the central nervous system (CNS). Reports on this mode of stem cell delivery have not yet focused on the route across the cribriform plate by which cells move from the nasal cavity into the CNS. In the current experiments, h...

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Main Authors: Carlos Galeano, Zhifang Qiu, Anuja Mishra, Steven L. Farnsworth, Jacob J. Hemmi, Alvaro Moreira, Peter Edenhoffer, Peter J. Hornsby
Format: Article
Language:English
Published: SAGE Publishing 2018-03-01
Series:Cell Transplantation
Online Access:https://doi.org/10.1177/0963689718754561
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author Carlos Galeano
Zhifang Qiu
Anuja Mishra
Steven L. Farnsworth
Jacob J. Hemmi
Alvaro Moreira
Peter Edenhoffer
Peter J. Hornsby
author_facet Carlos Galeano
Zhifang Qiu
Anuja Mishra
Steven L. Farnsworth
Jacob J. Hemmi
Alvaro Moreira
Peter Edenhoffer
Peter J. Hornsby
author_sort Carlos Galeano
collection DOAJ
description Intranasal administration is a promising route of delivery of stem cells to the central nervous system (CNS). Reports on this mode of stem cell delivery have not yet focused on the route across the cribriform plate by which cells move from the nasal cavity into the CNS. In the current experiments, human mesenchymal stem cells (MSCs) were isolated from Wharton’s jelly of umbilical cords and were labeled with extremely bright quantum dots (QDs) in order to track the cells efficiently. At 2 h after intranasal delivery in immunodeficient mice, the labeled cells were found under the olfactory epithelium, crossing the cribriform plate adjacent to the fila olfactoria, and associated with the meninges of the olfactory bulb. At all times, the cells were separate from actual nerve tracts; this location is consistent with them being in the subarachnoid space (SAS) and its extensions through the cribriform plate into the nasal mucosa. In their location under the olfactory epithelium, they appear to be within an expansion of a potential space adjacent to the turbinate bone periosteum. Therefore, intranasally administered stem cells appear to cross the olfactory epithelium, enter a space adjacent to the periosteum of the turbinate bones, and then enter the SAS via its extensions adjacent to the fila olfactoria as they cross the cribriform plate. These observations should enhance understanding of the mode by which stem cells can reach the CNS from the nasal cavity and may guide future experiments on making intranasal delivery of stem cells efficient and reproducible.
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spelling doaj.art-1a9e27645f5a425bb358d80981ef5a9f2022-12-21T23:53:42ZengSAGE PublishingCell Transplantation0963-68971555-38922018-03-012710.1177/0963689718754561The Route by Which Intranasally Delivered Stem Cells Enter the Central Nervous SystemCarlos Galeano0Zhifang Qiu1Anuja Mishra2Steven L. Farnsworth3Jacob J. Hemmi4Alvaro Moreira5Peter Edenhoffer6Peter J. Hornsby7 Department of Cellular and Integrative Physiology and Barshop Institute, University of Texas Health Science Center, San Antonio, TX, USA Department of Cellular and Integrative Physiology and Barshop Institute, University of Texas Health Science Center, San Antonio, TX, USA Department of Cellular and Integrative Physiology and Barshop Institute, University of Texas Health Science Center, San Antonio, TX, USA Department of Cellular and Integrative Physiology and Barshop Institute, University of Texas Health Science Center, San Antonio, TX, USA Department of Cellular and Integrative Physiology and Barshop Institute, University of Texas Health Science Center, San Antonio, TX, USA Department of Cellular and Integrative Physiology and Barshop Institute, University of Texas Health Science Center, San Antonio, TX, USA Department of Cellular and Integrative Physiology and Barshop Institute, University of Texas Health Science Center, San Antonio, TX, USA Department of Cellular and Integrative Physiology and Barshop Institute, University of Texas Health Science Center, San Antonio, TX, USAIntranasal administration is a promising route of delivery of stem cells to the central nervous system (CNS). Reports on this mode of stem cell delivery have not yet focused on the route across the cribriform plate by which cells move from the nasal cavity into the CNS. In the current experiments, human mesenchymal stem cells (MSCs) were isolated from Wharton’s jelly of umbilical cords and were labeled with extremely bright quantum dots (QDs) in order to track the cells efficiently. At 2 h after intranasal delivery in immunodeficient mice, the labeled cells were found under the olfactory epithelium, crossing the cribriform plate adjacent to the fila olfactoria, and associated with the meninges of the olfactory bulb. At all times, the cells were separate from actual nerve tracts; this location is consistent with them being in the subarachnoid space (SAS) and its extensions through the cribriform plate into the nasal mucosa. In their location under the olfactory epithelium, they appear to be within an expansion of a potential space adjacent to the turbinate bone periosteum. Therefore, intranasally administered stem cells appear to cross the olfactory epithelium, enter a space adjacent to the periosteum of the turbinate bones, and then enter the SAS via its extensions adjacent to the fila olfactoria as they cross the cribriform plate. These observations should enhance understanding of the mode by which stem cells can reach the CNS from the nasal cavity and may guide future experiments on making intranasal delivery of stem cells efficient and reproducible.https://doi.org/10.1177/0963689718754561
spellingShingle Carlos Galeano
Zhifang Qiu
Anuja Mishra
Steven L. Farnsworth
Jacob J. Hemmi
Alvaro Moreira
Peter Edenhoffer
Peter J. Hornsby
The Route by Which Intranasally Delivered Stem Cells Enter the Central Nervous System
Cell Transplantation
title The Route by Which Intranasally Delivered Stem Cells Enter the Central Nervous System
title_full The Route by Which Intranasally Delivered Stem Cells Enter the Central Nervous System
title_fullStr The Route by Which Intranasally Delivered Stem Cells Enter the Central Nervous System
title_full_unstemmed The Route by Which Intranasally Delivered Stem Cells Enter the Central Nervous System
title_short The Route by Which Intranasally Delivered Stem Cells Enter the Central Nervous System
title_sort route by which intranasally delivered stem cells enter the central nervous system
url https://doi.org/10.1177/0963689718754561
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