| First Author | Burks SR | Year | 2018 |
| Journal | J Cell Mol Med | Volume | 22 |
| Issue | 12 | Pages | 6015-6025 |
| PubMed ID | 30216653 | Mgi Jnum | J:295656 |
| Mgi Id | MGI:6454181 | Doi | 10.1111/jcmm.13874 |
| Citation | Burks SR, et al. (2018) Mesenchymal stromal cell potency to treat acute kidney injury increased by ultrasound-activated interferon-gamma/interleukin-10 axis. J Cell Mol Med 22(12):6015-6025 |
| abstractText | 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-gamma (IFNgamma) and stimulates MSC to produce interleukin-10 (IL-10) after migrating to kidneys. To demonstrate initially, MSC cultured with IFNgamma up-regulated IL-10. More MSC-derived IL-10 was detected in kidneys when IFNgamma-stimulated MSC were infused and they improved AKI better than unstimulated MSC. Next, IFNgamma-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 IFNgamma, 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 IFNgamma is up-regulated by pFUS and after i.v.-infused MSC home to pFUS-treated kidneys, IFNgamma stimulates additional IL-10 production by MSC to improve AKI. Analogous mechanisms of ultrasound-treated tissue microenvironments stimulating therapeutic MSC may exist in other pathologies where adjuvant ultrasound techniques are successful. |
