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Series GSE82269 Query DataSets for GSE82269
Status Public on May 23, 2017
Title Shear stress induces immunomodulatory signaling in bone marrow mesenchymal stromal cells (MSCs)
Organism Homo sapiens
Experiment type Expression profiling by array
Summary Bone marrow mesenchymal stromal cells (MSCs) regulate homeostasis and trafficking of cells of the blood lineage. In response to traumatic injury or infection, MSCs are believed to mobilize from the bone marrow, but it is largely unknown how egress into circulation impacts MSC function. Here we show that biomechanical forces associated with trafficking of MSCs from the bone marrow into the vasculature contribute uniquely to genetic signaling that reinforces MSC repression of immune cell activation. Laminar wall shear stress (LSS) typical of fluid frictional forces present on the lumen of arterioles stimulates increases in antioxidant and anti-inflammatory mediators, as well as an array of chemokines capable of immune cell recruitment. Importantly, LSS promotes a signaling cascade through COX2 that elevates prostaglandin E2 (PGE2) biosynthesis, permitting MSCs to suppress immune cell activation in the presence of inflammatory cues. Pharmacological inhibition of COX2 depleted PGE2 and impaired the ability of MSCs to block tumor necrosis factor-α (TNF-α) production, supporting a key role for PGE2 in the MSC immunomodulatory response to LSS. Preconditioning of MSCs by LSS ex vivo was an effective means of enhancing therapeutic efficacy in a rat model of traumatic brain injury, as evidenced by decreased numbers of apoptotic and M1-type activated microglia in the hippocampus and by retention of endogenous MSCs in the bone marrow. We conclude that biomechanical forces provide critical cues to MSCs residing at the vascular interface which influence MSC immunomodulatory and paracrine functions, thus providing unique opportunities for functional enhancement of MSCs used in therapeutic applications.
 
Overall design We hypothesized that fluid shear stress caused by vascular flow might alter mesenchymal stromal cell (MSC) signaling and function. To mimic arterial force at the vascular wall, we cultured human bone marrow-derived MSCs in microfluidics capable of producing uniform laminar flow at a wall shear stress (LSS) of 15 dyne/cm^2. Bone marrow MSCs were derived from whole bone marrow from independent human donors (AllCells). Cells were passaged into microfluidic IBIDI channels (μ-Slide VI 0.4) at a density of 3x10^6 cells/ml and permitted to attach to the culture surface for 18 hours. Following attachment, a peristaltic pump (REGLO analog MS4/12, Ismatec) was used to produce LSS of 15 dyne/cm2 for 6 hours. Lysis for RNA isolation was conducted immediately after LSS within the microfluidics.
 
Contributor(s) Wenzel PL
Citation(s) 28181347
NIH grant(s)
Grant ID Grant title Affiliation Name
K01 DK092365 Identification of biomechanical pathways that promote hematopoiesis UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON PAMELA LYNN WENZEL
Submission date Jun 04, 2016
Last update date Aug 13, 2018
Contact name Pamela L Wenzel
Organization name University of Texas Medical School at Houston
Department Pediatric Surgery
Lab Pamela Wenzel
Street address 1825 Pressler St, SRB637A
City Houston
State/province TX
ZIP/Postal code 77030
Country USA
 
Platforms (1)
GPL10558 Illumina HumanHT-12 V4.0 expression beadchip
Samples (6)
GSM2187307 Bone marrow MSC 3388 Static
GSM2187308 Bone marrow MSC 3388 LSS
GSM2187309 Bone marrow MSC 3390 Static
Relations
BioProject PRJNA324489

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Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE82269_Non-normalized_data.txt.gz 1.2 Mb (ftp)(http) TXT
GSE82269_RAW.tar 38.5 Mb (http)(custom) TAR (of IDAT)
SRA Run SelectorHelp
Raw data provided as supplementary file
Processed data included within Sample table
Raw data is available on Series record

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