Intranasal Delivery of Bone Marrow-Derived Mesenchymal Stem Cells, Macrophages, and Microglia to the Brain in Mouse Models of Alzheimer's and Parkinson's Disease

Danielyan, Lusine; Beer‐Hammer, Sandra; Stolzing, Alexandra; Schäfer, Richard; Siegel, Georg; Fabian, Claire; Kahle, Philipp J.; Biedermann, Tilo; Lourhmati, Ali; Buadze, Marine; Novakovic, Ana; Proksch, Barbara; Gleiter, Christoph H.; Frey, William H.; Schwab, Matthias

doi:10.3727/096368914x684970

Cited by 129 publications

(83 citation statements)

References 77 publications

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“…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. Currently, no side effects observed in stem cell transplantation via intranasal administration.…”

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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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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“…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).…”

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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“…Finally, intranasal delivery of drugs, nucleic acids, and cells through the olfactory conduit to the CNS will drastically improve therapeutic and prophylactic approaches to neurological and neuropsychiatric diseases in the future (Dhuria et al, 2010;Kanazawa T et al, 2013;Danielyan et al, 2014).…”

Section: Discussionmentioning

confidence: 99%

Transolfactory neuroinvasion by viruses threatens the human brain

Mori¹

2015

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Summary. -Viral neuroinvasion via the olfactory system has been investigated in a variety of virus-animal models by scientists in many fi elds including virologists, pathologists, and neurologists. In humans, herpes simplex virus type 1 (HSV-1), human herpesvirus 6 (HHV-6), Borna disease virus, rabies virus, and infl uenza A virus have been shown to take the olfactory route for neuroinvasion based on forensic and post-mortem specimens. Th is article briefl y summarizes the anatomy, physiology, and immunology of the olfactory system and presents a battery of neurovirulent viruses that may threaten the human brain by invading through this peripheral pathway, especially focusing on two of the most intensively studied viruses -HSV-1 and infl uenza A virus. Viruses may insidiously invade the olfactory neural network not only to precipitate encephalitis/encephalopathy but also to promote the development of neurodegenerative and demyelinating disorders. Substantial information obtained by analyzing human specimens is required to argue for or against this hypothesis.Keywords: virus; olfactory neuron; human brain; encephalitis; neurodegenerative disorders Acta virologica 59: 338 -349, 2015 doi:10.4149/av_2015_04_338 E-mail: mori@shubun-ac.jp; phone: +81-586-45-2101 Abbreviations: CNS = central nervous system; CSF = cerebrospinal fl uid; HHV-6 = human herpesvirus 6; HPAI = highly pathogenic avian infl uenza; HSE = herpes simplex encephalitis; HSV-1 = herpes simplex virus type 1; IFN = interferon; ORNs = olfactory receptor neurons; RIG-1 = retinoic acid inducible gene 1; TLR3 = toll-like receptor 3

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Intranasal Delivery of Bone Marrow-Derived Mesenchymal Stem Cells, Macrophages, and Microglia to the Brain in Mouse Models of Alzheimer's and Parkinson's Disease

Cited by 129 publications

References 77 publications

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

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

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

Transolfactory neuroinvasion by viruses threatens the human brain

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