Anti-inflammatory drugs suppress ultrasound-mediated mesenchymal stromal cell tropism to kidneys

Abstract Mesenchymal stromal cells (MSC) are potential renal therapeutics. Clinically, results are mixed partly because MSC tropism to kidneys is minimal following infusion. Ultrasound augmentation of the renal microenvironment is becoming increasingly-important in renal MSC therapies. We demonstrat...

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Autores principales:	Scott R. Burks, Ben A. Nguyen, Michele N. Bresler, Matthew E. Nagle, Saejeong J. Kim, Joseph A. Frank
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/e17a4fdb4d774efe834c4097a6cba931
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spelling	oai:doaj.org-article:e17a4fdb4d774efe834c4097a6cba9312021-12-02T16:06:34ZAnti-inflammatory drugs suppress ultrasound-mediated mesenchymal stromal cell tropism to kidneys10.1038/s41598-017-08887-x2045-2322https://doaj.org/article/e17a4fdb4d774efe834c4097a6cba9312017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-08887-xhttps://doaj.org/toc/2045-2322Abstract Mesenchymal stromal cells (MSC) are potential renal therapeutics. Clinically, results are mixed partly because MSC tropism to kidneys is minimal following infusion. Ultrasound augmentation of the renal microenvironment is becoming increasingly-important in renal MSC therapies. We demonstrated pulsed-focused-ultrasound (pFUS) increases enhanced homing permeability and retention of MSC in mouse kidneys. Here, we characterized the temporal proteomic response to pFUS in mouse kidneys and its association with MSC tropism. pFUS induced molecular cascades of initial increases in tumor necrosis factor-α (TNFα) and interleukin (IL)-1α, that activated nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB) and cyclooxygenase-2 (COX2) pathways without cell death. This was followed by a 24–48 hour-long response of increased cell adhesion molecules (CAM), trophic and anti-inflammatory factors. Pretreating animals with anti-inflammatory drugs etanercept (TNFα inhibitor), anakinra (IL-1 receptor antagonist), prednisone (NFκB translocation inhibitor), or ibuprofen (COX inhibitor) suppressed molecular changes and inhibited renal MSC tropism. We further examined the role of COX2 using a COX2-knock-out mouse where pFUS was unable to increase MSC tropism. These results demonstrate that renal micro-environmental changes induce MSC tropism and could influence the therapeutic efficacy of MSC. Optimizing the microenvironment and understanding drug effects will enable improvements in MSC therapies for renal disease.Scott R. BurksBen A. NguyenMichele N. BreslerMatthew E. NagleSaejeong J. KimJoseph A. FrankNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-9 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Scott R. Burks Ben A. Nguyen Michele N. Bresler Matthew E. Nagle Saejeong J. Kim Joseph A. Frank Anti-inflammatory drugs suppress ultrasound-mediated mesenchymal stromal cell tropism to kidneys
description	Abstract Mesenchymal stromal cells (MSC) are potential renal therapeutics. Clinically, results are mixed partly because MSC tropism to kidneys is minimal following infusion. Ultrasound augmentation of the renal microenvironment is becoming increasingly-important in renal MSC therapies. We demonstrated pulsed-focused-ultrasound (pFUS) increases enhanced homing permeability and retention of MSC in mouse kidneys. Here, we characterized the temporal proteomic response to pFUS in mouse kidneys and its association with MSC tropism. pFUS induced molecular cascades of initial increases in tumor necrosis factor-α (TNFα) and interleukin (IL)-1α, that activated nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB) and cyclooxygenase-2 (COX2) pathways without cell death. This was followed by a 24–48 hour-long response of increased cell adhesion molecules (CAM), trophic and anti-inflammatory factors. Pretreating animals with anti-inflammatory drugs etanercept (TNFα inhibitor), anakinra (IL-1 receptor antagonist), prednisone (NFκB translocation inhibitor), or ibuprofen (COX inhibitor) suppressed molecular changes and inhibited renal MSC tropism. We further examined the role of COX2 using a COX2-knock-out mouse where pFUS was unable to increase MSC tropism. These results demonstrate that renal micro-environmental changes induce MSC tropism and could influence the therapeutic efficacy of MSC. Optimizing the microenvironment and understanding drug effects will enable improvements in MSC therapies for renal disease.
format	article
author	Scott R. Burks Ben A. Nguyen Michele N. Bresler Matthew E. Nagle Saejeong J. Kim Joseph A. Frank
author_facet	Scott R. Burks Ben A. Nguyen Michele N. Bresler Matthew E. Nagle Saejeong J. Kim Joseph A. Frank
author_sort	Scott R. Burks
title	Anti-inflammatory drugs suppress ultrasound-mediated mesenchymal stromal cell tropism to kidneys
title_short	Anti-inflammatory drugs suppress ultrasound-mediated mesenchymal stromal cell tropism to kidneys
title_full	Anti-inflammatory drugs suppress ultrasound-mediated mesenchymal stromal cell tropism to kidneys
title_fullStr	Anti-inflammatory drugs suppress ultrasound-mediated mesenchymal stromal cell tropism to kidneys
title_full_unstemmed	Anti-inflammatory drugs suppress ultrasound-mediated mesenchymal stromal cell tropism to kidneys
title_sort	anti-inflammatory drugs suppress ultrasound-mediated mesenchymal stromal cell tropism to kidneys
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/e17a4fdb4d774efe834c4097a6cba931
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Anti-inflammatory drugs suppress ultrasound-mediated mesenchymal stromal cell tropism to kidneys

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