TY - JOUR
T1 - The Route by Which Intranasally Delivered Stem Cells Enter the Central Nervous System
AU - Galeano, Carlos
AU - Qiu, Zhifang
AU - Mishra, Anuja
AU - Farnsworth, Steven L.
AU - Hemmi, Jacob J.
AU - Moreira, Alvaro
AU - Edenhoffer, Peter
AU - Hornsby, Peter J.
N1 - Funding Information:
The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by VA Merit Grant I01 BX001454, by a grant from the Owens Medical Foundation, by grant R03 AG045481 from the National Institute on Aging, and by grant P51 OD011133 (Southwest National Primate Research Center).
Publisher Copyright:
© 2018, The Author(s) 2018.
PY - 2018/3/1
Y1 - 2018/3/1
N2 - 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.
AB - 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.
KW - Wharton’s jelly
KW - central nervous system
KW - mesenchymal stem cells
KW - nanoparticles/nanotechnology
KW - olfactory mucosa
KW - xenotransplantation
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U2 - 10.1177/0963689718754561
DO - 10.1177/0963689718754561
M3 - Article
C2 - 29756518
AN - SCOPUS:85048283275
VL - 27
SP - 501
EP - 514
JO - Cell Transplantation
JF - Cell Transplantation
SN - 0963-6897
IS - 3
ER -