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Monocyte Trafficking, Engraftment, and Delivery of Nanoparticles and an Exogenous Gene into the Acutely Inflamed Brain Tissue - Evaluations on Monocyte-Based Delivery System for the Central Nervous System
Tong, Hsin-I1,2; Kang, Wen1,4; Davy, Philip M. C.3; Shi, Yingli1,5; Sun, Si1; Allsopp, Richard C.3; Lu, Yuanan1
2016-04-26
Source PublicationPLOS ONE
Volume11Issue:4
SubtypeArticle
AbstractThe ability of monocytes and monocyte-derived macrophages (MDM) to travel towards chemotactic gradient, traverse tissue barriers, and accumulate precisely at diseased sites makes them attractive candidates as drug carriers and therapeutic gene delivery vehicles targeting the brain, where treatments are often hampered by the blockade of the blood brain barrier (BBB). This study was designed to fully establish an optimized cell-based delivery system using monocytes and MDM, by evaluating their homing efficiency, engraftment potential, as well as carriage and delivery ability to transport nano-scaled particles and exogenous genes into the brain, following the non-invasive intravenous (IV) cell adoptive transfer in an acute neuroinflammation mouse model induced by intracranial injection of Escherichia coli lipopolysaccharides. We demonstrated that freshly isolated monocytes had superior inflamed-brain homing ability over MDM cultured in the presence of macrophage colony stimulating factor. In addition, brain trafficking of IV infused monocytes was positively correlated with the number of adoptive transferred cells, and could be further enhanced by transient disruption of the BBB with IV administration of Mannitol, Bradykinin or Serotonin right before cell infusion. A small portion of transmigrated cells was detected to differentiate into IBA-1 positive cells with microglia morphology in the brain. Finally, with the use of superparamagnetic iron oxide nanoparticles SHP30, the ability of nanoscale agent-carriage monocytes to enter the inflamed brain region was validated. In addition, lentiviral vector DHIV-101 was used to introduce green fluorescent protein (GFP) gene into monocytes, and the exogenous GFP gene was detected in the brain at 48 hours following IV infusion of the transduced monocytes. All together, our study has set up the optimized conditions for the more-in-depth tests and development of monocyte-mediated delivery, and our data supported the notion to use monocytes as a non-invasive cell-based delivery system for the brain.
DOI10.1371/journal.pone.0154022
Indexed BySCI
Language英语
WOS IDWOS:000374973600036
Citation statistics
Document Type期刊论文
Version出版稿
Identifierhttp://ir.qdio.ac.cn/handle/337002/131018
Collection实验海洋生物学重点实验室
Affiliation1.Univ Hawaii Manoa, Off Publ Hlth Studies, Honolulu, HI 96822 USA
2.Univ Hawaii Manoa, Dept Microbiol, Honolulu, HI 96822 USA
3.Univ Hawaii Manoa, Inst Biogenesis Res, Honolulu, HI 96822 USA
4.Fourth Mil Med Univ, Tangdu Hosp, Dept Infect Dis, Xian 710032, Shaanxi, Peoples R China
5.Chinese Acad Sci, Inst Oceanol, Qingdao, Shandong, Peoples R China
Recommended Citation
GB/T 7714
Tong, Hsin-I,Kang, Wen,Davy, Philip M. C.,et al. Monocyte Trafficking, Engraftment, and Delivery of Nanoparticles and an Exogenous Gene into the Acutely Inflamed Brain Tissue - Evaluations on Monocyte-Based Delivery System for the Central Nervous System[J]. PLOS ONE,2016,11(4).
APA Tong, Hsin-I.,Kang, Wen.,Davy, Philip M. C..,Shi, Yingli.,Sun, Si.,...&Lu, Yuanan.(2016).Monocyte Trafficking, Engraftment, and Delivery of Nanoparticles and an Exogenous Gene into the Acutely Inflamed Brain Tissue - Evaluations on Monocyte-Based Delivery System for the Central Nervous System.PLOS ONE,11(4).
MLA Tong, Hsin-I,et al."Monocyte Trafficking, Engraftment, and Delivery of Nanoparticles and an Exogenous Gene into the Acutely Inflamed Brain Tissue - Evaluations on Monocyte-Based Delivery System for the Central Nervous System".PLOS ONE 11.4(2016).
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