Involvement of PI3K and ROCK signaling pathways in migration of bone marrow-derived mesenchymal stem cells through human brain microvascular endothelial cell monolayers

Lin, Meina; Shang, De-Shu; Sun, Wei; Li, Bo; Xu, Xin; Fang, Wen-Gang; Zhao, Wei‐Dong; Cao, Liu; Chen, Yuhua

doi:10.1016/j.brainres.2013.03.035

Cited by 41 publications

(34 citation statements)

References 37 publications

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“…Our study is the first study, to the best of our knowledge, to show that ROCK-shRNA facilitates MSC migration under mechanical milieus such as fluid shear. It has been proposed for static culture that blocking ROCK diminishes cytoskeletal tension which may lower the resistance to remodelling during migration [16,17]. A similar mechanism may be applied for the flow shear situation.…”

Section: Discussionmentioning

confidence: 99%

“…RhoA kinase (ROCK), the first downstream effector of Rho GTPases, is involved in actin filament formation, cytoskeletal tension-mediated cell morphology change and the resultant cell fate decision [15]. In migration, ROCK is thought to aid in the cell contraction process and may regulate transmigration through other cell layers [16]. ROCK has also been proposed to be a therapeutic target for disorders of the central nervous system, because inhibiting ROCK enhanced neural cell elongation, protrusion and migration [17].…”

Section: Introductionmentioning

confidence: 99%

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Fluid-flow-induced mesenchymal stem cell migration: role of focal adhesion kinase and RhoA kinase sensors

Riehl

Lee

et al. 2015

J. R. Soc. Interface.

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The study of mesenchymal stem cell (MSC) migration under flow conditions with investigation of the underlying molecular mechanism could lead to a better understanding and outcome in stem-cell-based cell therapy and regenerative medicine. We used peer-reviewed open source software to develop methods for efficiently and accurately tracking, measuring and processing cell migration as well as morphology. Using these tools, we investigated MSC migration under flow-induced shear and tested the molecular mechanism with stable knockdown of focal adhesion kinase (FAK) and RhoA kinase (ROCK). Under steady flow, MSCs migrated following the flow direction in a shear stress magnitude-dependent manner, as assessed by root mean square displacement and mean square displacement, motility coefficient and confinement ratio. Silencing FAK in MSCs suppressed morphology adaptation capability and reduced cellular motility for both static and flow conditions. Interestingly, ROCK silencing significantly increased migration tendency especially under flow. Blocking ROCK, which is known to reduce cytoskeletal tension, may lower the resistance to skeletal remodelling during the flowinduced migration. Our data thus propose a potentially differential role of focal adhesion and cytoskeletal tension signalling elements in MSC migration under flow shear.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Fluid-flow-induced mesenchymal stem cell migration: role of focal adhesion kinase and RhoA kinase sensors

Riehl

Lee

et al. 2015

J. R. Soc. Interface.

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“…According to recent report which showed transmigration of the mesenchymal stem cells across the BBB, 22 it is likely that some cells are able to enter the WT mice brains. However, labeled hASCs were shown much more in the brains of Tg mice than in those of WT mice (Fig.…”

Section: Resultsmentioning

confidence: 99%

In vivoimaging of human adipose-derived stem cells in Alzheimer’s disease animal model

Ahn

Kim

et al. 2013

J. Biomed. Opt

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Abstract. Stem cell therapy is a promising tool for the treatment of diverse conditions, including neurodegenerative diseases such as Alzheimer's disease (AD). To understand transplanted stem cell biology, in vivo imaging is necessary. Nanomaterial has great potential for in vivo imaging and several noninvasive methods are used, such as magnetic resonance imaging, positron emission tomography, fluorescence imaging (FI) and near-infrared FI. However, each method has limitations for in vivo imaging. To overcome these limitations, multimodal nanoprobes have been developed. In the present study, we intravenously injected human adipose-derived stem cells (hASCs) that were labeled with a multimodal nanoparticle, LEO-LIVE™-Magnoxide 675 or 797 (BITERIALS, Seoul, Korea), into Tg2576 mice, an AD mouse model. After sequential in vivo tracking using Maestro Imaging System, we found fluorescence signals up to 10 days after injection. We also found strong signals in the brains extracted from hASCtransplanted Tg2576 mice up to 12 days after injection. With these results, we suggest that in vivo imaging with this multimodal nanoparticle may provide a useful tool for stem cell tracking and understanding stem cell biology in other neurodegenerative diseases. © The Authors. Published by SPIE under a Creative Commons Attribution 3.0 Unported License. Distribution or reproduction of this work in whole or in part requires full attribution of the original publication, including its DOI.

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“…It seems that MSCs undergo a leukocyte-like multistep homing cascade (i.e., rolling, adhesion, and transmigration) to engage with endothelial cells (ECs) [145] . Some studies indicate that MSCs may induce the disassembly of tight junctions in HBMEC through ERK1/2, PI3K, and ROCK signaling pathways [146,147] . Since in vitro studies are performed using EC monolayers that do not fully recapitulate the in vivo BBB properties, further in vivo research is needed.…”

Section: Methods To Promote the Homing Of Mscs In The Treatment Of Cnmentioning

confidence: 99%

Strategies to improve the migration of mesenchymal stromal cells in cell therapy

Chen

et al. 2017

Transl. Neurosci. Clin.

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KEYWORDSMSCs; migration; cell therapy; engraftment efficiency; neurological disorder Mesenchymal stromal/stem cells (MSCs) are multipotent cells under consideration as a potential new therapy for a variety of inflammatory diseases including certain neurological disorders. It is generally thought that the efficacy of cell therapy in attenuating damage after ischemia, inflammation, or injury depends on the quantity of transplanted cells recruited to the target tissue. However, only a small number of systematically infused MSCs can effectively migrate to target sites, which significantly decreases the efficacy of exogenous cell-based therapy. In this review, we discuss specific factors influencing MSC migration, and summarize current strategies that effectively promote the motility of MSCs. In addition, we describe several protocols to improve the migration of stromal cells into the nervous system and, therefore, enhance the efficiency of engraftment as means of treating neurological disorders.Citation Li G, Hu Y, Chen Y, Tang Z. Strategies to improve the migration of mesenchymal stromal cells in cell therapy. Transl. Neurosci. Clin. 2017, 3(3): 159-175.

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Involvement of PI3K and ROCK signaling pathways in migration of bone marrow-derived mesenchymal stem cells through human brain microvascular endothelial cell monolayers

Cited by 41 publications

References 37 publications

Fluid-flow-induced mesenchymal stem cell migration: role of focal adhesion kinase and RhoA kinase sensors

Fluid-flow-induced mesenchymal stem cell migration: role of focal adhesion kinase and RhoA kinase sensors

In vivoimaging of human adipose-derived stem cells in Alzheimer’s disease animal model

Strategies to improve the migration of mesenchymal stromal cells in cell therapy

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