Open AccessPulsed Focused Ultrasound Pretreatment Improves Mesenchymal Stromal Cell Efficacy in Preventing and Rescuing Established Acute Kidney Injury in Mice
Author(s) -
Burks Scott R.,
Nguyen Ben A.,
Tebebi Pamela A.,
Kim Saejeong J.,
Bresler Michele N.,
Ziadloo Ali,
Street Jonathan M.,
Yuen Peter S. T.,
Star Robert A.,
Frank Joseph A.
Publication year - 2015
Publication title -
stem cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.159
H-Index - 229
eISSN - 1549-4918
pISSN - 1066-5099
DOI - 10.1002/stem.1965
Subject(s) - homing (biology) , mesenchymal stem cell , acute kidney injury , medicine , stromal cell , cisplatin , cell therapy , kidney , cancer research , pathology , pharmacology , cell , biology , chemotherapy , ecology , genetics
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. S tem C ells 2015;33:1241–1253