Preliminary Study on the Method of Nasal Administration for Neural Stem Cells in SD Rats
Huang Ying1, Xiao Yani1, Wang Chao1, Qin Chao1, Huo Yan1, Zheng Jiawei2
Author information+
(1)National Center for Safety Evaluation of Drugs, National Institutes for Food and Drug Control, The Beijing Key Lab for Pre-clinical Safety Evaluation of Drugs, Beijing 100176 , China; (2)Shanghai Angecon Biotechnology Corporation, Shanghai 201203 , China
{{custom_zuoZheDiZhi}}
{{custom_authorNodes}}
{{custom_bio.content}}
{{custom_bio.content}}
{{custom_authorNodes}}
Collapse
History+
Issue Date
2022-08-11
Abstract
Objective: To establish a preclinical drug administration method that can simulate a novel route of stem cell administration by intranasal administration in rats, so as to lay a foundation for the preclinical safety evaluation of stem cells. Methods: Thirty-two Sprague Dawley (SD) rats were randomly divided into two groups- solvent control group and administration group, and sixteen animals were included in each group with half females and half males. Saline was administered to the solvent control group and human neural stem cells (NSCs) were administered to the administration group at a dose of 1×107 cells·kg-1. All animals were administrated intranasally once. 24 hours and 6 days after administration, the rats were anesthetized and their hearts were exposed. Blood was collected from the heart, the heart was perfused and fixed, the brain (striatum, substantia nigra, cortex, hippocampus, cerebellum), blood, heart, liver, spleen, lung, kidney, testis and epididymis (male) and ovary (female) were taken, and organs and tissues were fi xed. After taking materials, immunofluorescence experiments were carried out to study the biodistribution of NSCs in the above tissues and organs. Results: 24 hours and 6 days after intranasal administration of NSCs, the distribution of NSCs was observed in striatum, substantia nigra, cortex, hippocampus and cerebellum. No positive cells were found in peripheral tissues, including heart, liver, spleen, lung, kidney, testicle, epididymis (male), ovary (female) and peripheral blood. Conclusion: Our preclinical studies have shown that NSCs can be absorbed into the brain by nasal administration to treat brain diseases.
Huang Ying, Zheng Jiawei, Xiao Yani, Wang Chao, Qin Chao, Huo Yan.
Preliminary Study on the Method of Nasal Administration for Neural Stem Cells in SD Rats[J]. Chinese Pharmaceutical Affairs, 2022, 36(8): 954-959 https://doi.org/10.16153/j.1002-7777.2022.08.013
{{custom_sec.title}}
{{custom_sec.title}}
{{custom_sec.content}}
References
[1] Alzheimer's Association.Alzheimer's Disease Facts and Figures[J].Alzheimers & Dementia,2020，16（3）：391-460. [2] Aspelund A，Antila S，Proulx ST，et al.A Dural Lymphatic Vascular System that Drains Brain Interstitial Fluid and Macromolecules[J].J Exp Med，2015，212（7）：991-999． [3] 鞠爱春，耿诗涵，杨欣鹏，等．丹酚酸B鼻腔给药对脑缺血损伤大鼠学习记忆能力及神经再生的影响[J]．中草药，2017，48（12）：2481-2485． [4] 沈淼山，张苏宏，邱璐琦，等.壳聚糖神经毒素纳米粒鼻腔给药对血脑屏障开放性的影响[J].中草药，2017，48（12）：2461-2465． [5] Louveau A，Smirnov I，Keyes T J，et al．Structural and Functional Features of Central Nervous System Lymphatic Vessels[J].Nature，2015，523：337-341． [6] Ma Q，Ineichen BV，Detmar M，et al.Outflow of Cerebrospinal Fluid Is Predominantly Through Lymphatic Vessels and Is Reduced in Aged Mice[J].Nature Communications，2017，8（1）：1434． [7] Jafek BW.Ultrastructure of Uman Nasal Mucosa[J].Laryngoscope，1983，93（12）：1576-1599． [8] Thorne RG,Pronk GJ,Padmanabhan V,et al.Delivery of Insulin-like Growth Factor-I to the Rat Brain and Spinal Cord along Olfactory and Trigeminal Pathways following Intranasal Administration[J].Neuroscience，2004，127（2）：481-496. [9] Thorne RG，HansonL R，Ross TM，et al.Delivery of Interferon-beta to the Monkey Nervous System Following Intranasal Administration[J].Neuroscience，2008，152（3）：785-797. [10] Thorne RG,Emory CR,Ala TA，et al.Quantitative Analysis of the Olfactory Pathway for Drug Delivery to the Brain[J].Brain Res，1995，692（1-2）：278-282.[1 1] D o t y R L.T h e O l f a c t o r y V e c t o r H y p o t h e s i s o f Neurodegenerative Disease:Is It Viable[J].Ann NeuroL，2008，63（1）：7-15. [12] Kristensson K，Olsson Y.Uptake of Exogenous Proteins in Mouse Olfactory Cells[J].Acta Neuropathol，1971，19（2）：145-154. [13] Broadwell RD，Balin BJ.Endocytic and Exocytic Pathways of the Neuronal Secretory Process and Transsynaptic Transfer of Wheat Germ Agglutinin-horseradish Peroxidase in Vivo[J].J Comp Neurol，1985，242（4）：632-650. [14] Baker H，Spencer RF.Transneuronal Transport of Peroxidase-conjugated Wheat Germ Agglutinin(WGAHRP)from the Olfactory Epithelium to the Brain of the Adult Rat[J].Experimental Brain Research，1986，63（3）：461-473. [15] Kristensson K.Microbes' Roadmap to Neurons[J].Nature Reviews Neuroscience，2011，12（6）：345-357. [16] Deatly AM，Haase AT，Fewster PH，et al.Human Herpes Virus Infections and Alzheimer's Disease[J].Neuropathology and Applied Neurobiology，1990，16（3）：213-223. [17] Jin Y，Dons L，Kristensson K，et al.Neural Route of Cerebral Listeria Monocytogenes Murine Infection:Role of Immune Response Mechanisms in Controlling Bacterial Neuroinvasion[J].Infect Immun，2001，69（2）：1093-1100.
