Mesenchymal stromal cell potency to treat acute kidney injury increased by ultrasound-activated interferon-γ/interleukin-10 axis

Journal of Cellular and Molecular Medicine
Scott R BurksJoseph A Frank

Abstract

Mesenchymal stromal cell (MSC) therapies combined with renal pulsed focused ultrasound (pFUS) pretreatment increase MSC homing and improve cisplatin-induced acute kidney injury (AKI) better than MSC alone. However, mechanisms underlying improved outcomes remain unknown. We hypothesize pFUS up-regulates renal interferon-γ (IFNγ) and stimulates MSC to produce interleukin-10 (IL-10) after migrating to kidneys. To demonstrate initially, MSC cultured with IFNγ up-regulated IL-10. More MSC-derived IL-10 was detected in kidneys when IFNγ-stimulated MSC were infused and they improved AKI better than unstimulated MSC. Next, IFNγ-knockout mice with AKI received pFUS+MSC, but MSC-derived IL-10 expression and AKI were similar to using MSC alone. AKI in wild-type mice receiving pFUS and IL-10-deficient MSC was also unimproved compared to administering IL-10-deficient MSC alone. Indoleamine 2,3-dioxygenase (IDO), an anti-inflammatory enzyme up-regulated in MSC by IFNγ, was up-regulated during AKI, but was not further elevated in MSC from pFUS-treated kidneys, suggesting that IDO is not involved in improved AKI healing by pFUS+MSC. These data suggest IFNγ is up-regulated by pFUS and after i.v.-infused MSC home to pFUS-treated kidneys, IFNγ st...Continue Reading

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Citations

Mar 12, 2020·Stem Cells Translational Medicine·Daniel D LiuAvnesh S Thakor
Jun 27, 2020·Stem Cell Research & Therapy·Dongwei LiuZhangsuo Liu
Oct 18, 2020·Journal of Cellular and Molecular Medicine·Kee W JangJoseph A Frank
May 24, 2019·IScience·Mujib UllahAvnesh S Thakor
Jun 3, 2021·International Journal of Molecular Sciences·Raphael Rodrigues CorrêaRafael Soares Lindoso
Apr 30, 2020·Molecular Therapy. Methods & Clinical Development·Mujib UllahAvnesh S Thakor
Sep 30, 2021·Experimental and Therapeutic Medicine·Anamaria Magdalena TomşaLia Monica Junie

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Methods Mentioned

BETA
transgenic
transfection
electrophoresis
ELISA

Clinical Trials Mentioned

NCT01071577
NCT01275612

Software Mentioned

pFUS
ImageJ
Prism

Related Concepts

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