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

2018 ◽  
Vol 27 (3) ◽  
pp. 501-514 ◽  
Author(s):  
Carlos Galeano ◽  
Zhifang Qiu ◽  
Anuja Mishra ◽  
Steven L. Farnsworth ◽  
Jacob J. Hemmi ◽  
...  

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.

Author(s):  
Prithiv K R Kumar

Stem cells have the capacity to differentiate into any type of cell or organ. Stems cell originate from any part of the body, including the brain. Brain cells or rather neural stem cells have the capacitive advantage of differentiating into the central nervous system leading to the formation of neurons and glial cells. Neural stem cells should have a source by editing DNA, or by mixings chemical enzymes of iPSCs. By this method, a limitless number of neuron stem cells can be obtained. Increase in supply of NSCs help in repairing glial cells which in-turn heal the central nervous system. Generally, brain injuries cause motor and sensory deficits leading to stroke. With all trials from novel therapeutic methods to enhanced rehabilitation time, the economy and quality of life is suppressed. Only PSCs have proven effective for grafting cells into NSCs. Neurons derived from stem cells is the only challenge that limits in-vitro usage in the near future.


2022 ◽  
Vol 12 ◽  
Author(s):  
Johannes Flamm ◽  
Sunniva Hartung ◽  
Stella Gänger ◽  
Frank Maigler ◽  
Claudia Pitzer ◽  
...  

We have recently developed a region-specific catheter-based intranasal application method in mice by using CT scan-based 3D cast models of the murine nose (DOI: 10.2376/0005-9366-17,102). This technique is able to specifically deliver drugs to the olfactory region or to the respiratory region only. Thereby, intranasally administered drugs could be delivered either via neuronal connections to the central nervous system or via the well-perfused rostral parts of the nasal mucosa to the systemic circulation. In the present study, we transferred successfully this novel delivery technique to C57Bl/6 mice and determined parameters such as insertions depth of the catheter and maximum delivery volume in dependence to the weight of the mouse. Breathing was simulated to verify that the volume remains at the targeted area. A step-by-step procedure including a video is presented to adopt this technique for standardized and reproducible intranasal central nervous system (CNS) delivery studies (DOI: 10.3390/pharmaceutics13111904).


mSphere ◽  
2017 ◽  
Vol 2 (3) ◽  
Author(s):  
Viktoriya Borisevich ◽  
Mehmet Hakan Ozdener ◽  
Bilal Malik ◽  
Barry Rockx

ABSTRACT Henipaviruses are emerging zoonotic pathogens that can cause acute and severe respiratory and neurological disease in humans. The pathways by which henipaviruses enter the central nervous system (CNS) in humans are still unknown. The observation that human olfactory neurons are highly susceptible to infection with henipaviruses demonstrates that the olfactory epithelium can serve as a site of Henipavirus entry into the CNS. Henipaviruses are emerging zoonotic viruses and causative agents of encephalitis in humans. However, the mechanisms of entry into the central nervous system (CNS) in humans are not known. Here, we evaluated the possible role of olfactory epithelium in virus entry into the CNS. We characterized Hendra virus (HeV) and Nipah virus (NiV) infection of primary human olfactory epithelial cultures. We show that henipaviruses can infect mature olfactory sensory neurons. Henipaviruses replicated efficiently, resulting in cytopathic effect and limited induction of host responses. These results show that human olfactory epithelium is susceptible to infection with henipaviruses, suggesting that this could be a pathway for neuroinvasion in humans. IMPORTANCE Henipaviruses are emerging zoonotic pathogens that can cause acute and severe respiratory and neurological disease in humans. The pathways by which henipaviruses enter the central nervous system (CNS) in humans are still unknown. The observation that human olfactory neurons are highly susceptible to infection with henipaviruses demonstrates that the olfactory epithelium can serve as a site of Henipavirus entry into the CNS.


2019 ◽  
Vol 20 (17) ◽  
pp. 4123 ◽  
Author(s):  
Diana ◽  
Gaido ◽  
Murtas

MicroRNAs, also called miRNAs or simply miR-, represent a unique class of non-coding RNAs that have gained exponential interest during recent years because of their determinant involvement in regulating the expression of several genes. Despite the increasing number of mature miRNAs recognized in the human species, only a limited proportion is engaged in the ontogeny of the central nervous system (CNS). miRNAs also play a pivotal role during the transition of normal neural stem cells (NSCs) into tumor-forming NSCs. More specifically, extensive studies have identified some shared miRNAs between NSCs and neural cancer stem cells (CSCs), namely miR-7, -124, -125, -181 and miR-9, -10, -130. In the context of NSCs, miRNAs are intercalated from embryonic stages throughout the differentiation pathway in order to achieve mature neuronal lineages. Within CSCs, under a different cellular context, miRNAs perform tumor suppressive or oncogenic functions that govern the homeostasis of brain tumors. This review will draw attention to the most characterizing studies dealing with miRNAs engaged in neurogenesis and in the tumoral neural stem cell context, offering the reader insight into the power of next generation miRNA-targeted therapies against brain malignances.


2007 ◽  
Vol 18 (12) ◽  
pp. 1182-1192 ◽  
Author(s):  
Juyeon Jung ◽  
Neil R. Hackett ◽  
Robert G. Pergolizzi ◽  
Lorraine Pierre-Destine ◽  
Anja Krause ◽  
...  

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