Pulsed focused ultrasound pretreatment improves mesenchymal stromal cell efficacy in preventing and rescuing established acute kidney injury in mice
Authors: Ali Ziadloo
Ben A Nguyen
Peter S T Yuen
Michele N Bresler
Saejeong J Kim
Pamela A Tebebi
Scott R Burks
Jonathan M Street
Joseph A Frank
Robert A Star
Journal: Stem Cells (2015)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Acute kidney injury; Cellular therapy; Cisplatin; Kidney; Mesenchymal stromal cells
Affiliations: Frank Laboratory, Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, Bethesda, Maryland, USA; Imaging Sciences Training Program, Clinical Center and National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, Maryland, USA., Frank Laboratory, Radiology and Imaging Sciences, Clinical CenterNational Institutes of HealthBethesda Maryland USA, Department of Biomedical EngineeringThe Catholic University of AmericaWashington District of Columbia USA, Renal Diagnostics and Therapeutics Unit, Kidney Diseases BranchNational Institute of Diabetes and Digestive and Kidney DiseasesBethesda Maryland USA, Intramural Research ProgramNational Institute of Biomedical Imaging and BioengineeringBethesda Maryland USA

Abstract:  Animal studies have shown that mesenchymal stromal cell (MSC) infusions improve acute kidney injury (AKI) outcomes when administered early after ischemic/reperfusion injury or within 24 hours after cisplatin administration. These findings have spurred several human clinical trials to prevent AKI. However, no specific therapy effectively treats clinically obvious AKI or rescues renal function once advanced injury is established. We investigated if noninvasive image-guided pulsed focused ultrasound (pFUS) could alter the kidney microenvironment to enhance homing of subsequently infused MSC. To examine the efficacy of pFUS-enhanced cell homing in disease, we targeted pFUS to kidneys to enhance MSC homing after cisplatin-induced AKI. We found that pFUS enhanced MSC homing at 1 day post-cisplatin, prior to renal functional deficits, and that enhanced homing improved outcomes of renal function, tubular cell death, and regeneration at 5 days post-cisplatin compared to MSC alone. We then investigated whether pFUS+MSC therapy could rescue established AKI. MSC alone at 3 days post-cisplatin, after renal functional deficits were obvious, significantly improved 7-day survival of animals. Survival was further improved by pFUS and MSC. pFUS prior to MSC injections increased IL-10 production by MSC that homed to kidneys and generated an anti-inflammatory immune cell profile in treated kidneys. This study shows pFUS is a neoadjuvant approach to improve MSC homing to diseased organs. pFUS with MSC better prevents AKI than MSC alone and allows rescue therapy in established AKI, which currently has no meaningful therapeutic options. 

Retracted: No

PubPeer comments:
 Yet another new nonsensical paper generated using the forged definition of consistency of fuzzy preference relations. For example, it is cited in Definition 2 such a consistency definition with credit to Tanino. However, this version of consistency was not presented in Tanino (1984) but presented repeatedly by Zeshui Xu, a very prolific author in decision making of unconventional sense, and his co-authors. See the comment on the 2006 paper by J. Chen and Z. Xu (doi: 10.1016 j.ejor.2006.11.011) on https: pubpeer.com publications 7867CDD08E699F6D01C0E11F1693E0 This 2006 paper was not cited in this paper but a total of 9 papers by Z. Xu were included. However, they are all nonsensical according to the comments on https: pubpeer.com publications 2F6D7E7536F8BE6716F051849F57B3 https: pubpeer.com publications 0DA0DAD6721194EDE367D9AC1D6616 https: pubpeer.com publications 69F3B28A2854C1D6FF76EC3F2BF065 https: pubpeer.com publications D530678933C8E29B21BC89733B4C47 https: pubpeer.com publications 30814165353935C154DB0FBFFBB70A https: pubpeer.com publications A6D778B0BEBA86BFA549948CF753FA https: pubpeer.com publications A7DB065DCFF734D5B6DD95E7BDBF9B https: pubpeer.com publications DD6AEFC67EF1635397D0108992A627 https: pubpeer.com publications 71FDCC2D40BF323267FC9CC59A4B9F ![file] ,