Intranasal delivery of stem cells to the brain

Jiang, Yongjun; Zhu, Juehua; Xu, Gelin; Liu, Xinfeng

doi:10.1517/17425247.2011.566267

Cited by 80 publications

(52 citation statements)

References 78 publications

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“…The IN administration of therapeutic agents was attempted with numerous vehicles and tracking methodologies (29,30). In the majority of studies, IN administration (alone or assisted with drug delivery agents) successfully reached the intracranial region and led to significant improvement in the disease (31). In addition, investigation of the role of IN stem cell delivery in PD has been attempted in several animal models, with promising results.…”

Section: Discussionmentioning

confidence: 99%

Effect of intranasal stem cell administration on the nigrostriatal system in a mouse model of Parkinson's disease

Salama

Sobh

Emam

et al. 2017

Experimental and Therapeutic Medicine

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Abstract. Parkinson's disease (PD) is the second most common neurodegenerative disease worldwide. It affects the locomotor system, leading to a final severe disability through degeneration of dopaminergic neurons. Despite several therapeutic approaches used, no treatment has been proven to be effective; however, cell therapy may be a promising therapeutic method. In addition, the use of the intranasal (IN) route has been advocated for delivering various therapies to the brain. In the present study, the IN route was used for administration of mesenchymal stem cells (MSCs) in a mouse model of PD, with the aim to evaluate IN delivery as an alternative route for cell based therapy administration in PD. The PD model was developed in C57BL/6 mice using intraperitoneal rotenone administration for 60 consecutive days. MSCs were isolated from the mononuclear cell fraction of pooled bone marrow from C57BL/6 mice and incubated with micrometer-sized iron oxide (MPIO) particles. For IN administration, we used a 20 µl of 5x10 5 cell suspension. Neurobehavioral assessment of the mice was performed, and after sacrifice, brain sections were stained with Prussian blue to detect the MPIO-labeled MSCs. In addition, immunohistochemical evaluation was conducted to detect tyrosine hydroxylase (TH) antibodies in the corpus striatum and dopaminergic neurons in the substantia nigra pars compacta (SNpc). The neurobehavioral assessment revealed progressive deterioration in the locomotor functions of the rotenone group, which was improved following MSC administration. Histopathological evaluation of brain sections in the rotenone+MSC group revealed successful delivery of MSCs, evidenced by positive Prussian blue staining. Furthermore, rotenone treatment led to significant decrease in dopaminergic neuron number in SNpc, as well as similar decrease in the corpus striatum fiber density. By contrast, in animals receiving IN administration of MSCs, the degeneration caused by rotenone treatment was significantly counteracted. In conclusion, the present study validated that IN delivery of MSCs may be a potential safe, easy and cheap alternative route for stem cell treatment in neurodegenerative disorders.

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Section: Discussionmentioning

confidence: 99%

Effect of intranasal stem cell administration on the nigrostriatal system in a mouse model of Parkinson's disease

Salama

Sobh

Emam

et al. 2017

Experimental and Therapeutic Medicine

View full text Add to dashboard Cite

show abstract

“…In transgenic mice of Parkinson's disease (PD) and Alzheimer's disease (AD) models, MSCs were detected in the olfactory bulb (OB), cortex, amygdala, striatum, hippocampus, cerebellum, and brainstem after intranasal delivery, with majority of the MSCs found in the OB and the brainstem [135]. Although the mechanism of intranasal delivery was unclear, olfactory nerve pathways, trigeminal nerve pathways, vascular pathways, and lymphatic pathways were possibly involved [136]. The safeness and efficiency of intranasal administration in various neurological disorders including ischemic stroke [73], hypoxia-ischemia [137], experimental autoimmune encephalomyelitis (EAE) [135], AD, and PD [138,139] were investigated.…”

Section: Routes Of Transplantationmentioning

confidence: 99%

“…MSCs were used in studies mentioned above for intranasal delivery. Whether intranasal administration was safe and effective for other stem cells delivery such as NSCs, EPCs, and ESCs needed to be further tested [136].…”

Section: Routes Of Transplantationmentioning

confidence: 99%

Opportunities and Challenges: Stem Cell‐Based Therapy for the Treatment of Ischemic Stroke

Tang

Zhang

et al. 2015

CNS Neurosci Ther

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Stem cell-based therapy for ischemic stroke has been widely explored in animal models and provides strong evidence of benefits. In this review, we summarize the types of stem cells, various delivery routes, and tracking tools for stem cell therapy of ischemic stroke. MSCs, EPCs, and NSCs are the most explored cell types for ischemic stroke treatment. Although the mechanisms of stem cell-based therapies are not fully understood, the most possible functions of the transplanted cells are releasing growth factors and regulating microenvironment through paracrine mechanism. Clinical application of stem cell-based therapy is still in its infancy. The next decade of stem cell research in stroke field needs to focus on combining different stem cells and different imaging modalities to fully explore the potential of this therapeutic avenue: from bench to bedside and vice versa.

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“…Although intra-cerebroventricular injection can deliver drugs directly to the brain, it is highly invasive and so not feasible for clinical applications. Intranasal administration, in contrast, has been shown to directly achieve CNS delivery of a variety of compounds; 21,22 it rapidly increases CNS levels of these compounds, improves bioavailability, and has no peripherally induced adverse effects. It may, therefore, represent the most promising, novel, non-invasive method for delivering therapeutic substances directly to the CNS for the treatment of CNS disorders, such as MS, Alzheimer's disease, Parkinson's disease and Huntington's disease.…”

Section: M M U N O L O G Y O R I G I N a L A R T I C L Ementioning

confidence: 99%

Intranasal delivery of FSD‐C10, a novel Rho kinase inhibitor, exhibits therapeutic potential in experimental autoimmune encephalomyelitis

Liu

et al. 2014

Immunology

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SummaryViewing multiple sclerosis (MS) as both neuroinflammation and neurodegeneration has major implications for therapy, with neuroprotection and neurorepair needed in addition to controlling neuroinflammation in the central nervous system (CNS). While Fasudil, an inhibitor of Rho kinase (ROCK), is known to suppress experimental autoimmune encephalomyelitis (EAE), an animal model of MS, it relies on multiple, short-term injections, with a narrow safety window. In this study, we explored the therapeutic effect of a novel ROCK inhibitor FSD-C10, a Fasudil derivative, on EAE. An important advantage of this derivative is that it can be used via non-injection routes; intranasal delivery is the preferred route because of its efficient CNS delivery and the much lower dose compared with oral delivery. Our results showed that intranasal delivery of FSD-C10 effectively ameliorated the clinical severity of EAE and CNS inflammatory infiltration and promoted neuroprotection. FSD-C10 effectively induced CNS production of the immunoregulatory cytokine interleukin-10 and boosted expression of nerve growth factor and brain-derived neurotrophic factor proteins, while inhibiting activation of p-nuclear factor-jB/p65 on astrocytes and production of multiple pro-inflammatory cytokines. In addition, FSD-C10 treatment effectively induced CD4 + CD25 + , CD4 + FOXP3 + regulatory T cells. Together, our results demonstrate that intranasal delivery of the novel ROCK inhibitor FSD-C10 has therapeutic potential in EAE, through mechanisms that possibly involve both inhibiting CNS inflammation and promoting neuroprotection.

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Intranasal delivery of stem cells to the brain

Cited by 80 publications

References 78 publications

Effect of intranasal stem cell administration on the nigrostriatal system in a mouse model of Parkinson's disease

Effect of intranasal stem cell administration on the nigrostriatal system in a mouse model of Parkinson's disease

Opportunities and Challenges: Stem Cell‐Based Therapy for the Treatment of Ischemic Stroke

Intranasal delivery of FSD‐C10, a novel Rho kinase inhibitor, exhibits therapeutic potential in experimental autoimmune encephalomyelitis

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