MilliporeSigma
  • Home
  • Search Results
  • Pulsed focused ultrasound pretreatment improves mesenchymal stromal cell efficacy in preventing and rescuing established acute kidney injury in mice.

Pulsed focused ultrasound pretreatment improves mesenchymal stromal cell efficacy in preventing and rescuing established acute kidney injury in mice.

Stem cells (Dayton, Ohio) (2015-02-03)
Scott R Burks, Ben A Nguyen, Pamela A Tebebi, Saejeong J Kim, Michele N Bresler, Ali Ziadloo, Jonathan M Street, Peter S T Yuen, Robert A Star, Joseph A Frank
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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
trans-Platinum(II)diammine dichloride
Sigma-Aldrich
cis-Diammineplatinum(II) dichloride, crystalline
Sigma-Aldrich
L-Glutamine, ReagentPlus®, ≥99% (HPLC)
SAFC
L-Glutamine
Sigma-Aldrich
L-Glutamine, BioUltra, ≥99.5% (NT)
Supelco
Sodium Nitroprusside, Pharmaceutical Secondary Standard; Certified Reference Material
Cisplatin, European Pharmacopoeia (EP) Reference Standard
Sigma-Aldrich
L-Glutamine, meets USP testing specifications, suitable for cell culture, 99.0-101.0%, from non-animal source
Sigma-Aldrich
L-Glutamine, γ-irradiated, BioXtra, suitable for cell culture
Supelco
L-Glutamine, Pharmaceutical Secondary Standard; Certified Reference Material
Supelco
L-Glutamine, certified reference material, TraceCERT®
Sigma-Aldrich
L-Glutamine
USP
Transplatin, United States Pharmacopeia (USP) Reference Standard
Cisplatin impurity A, European Pharmacopoeia (EP) Reference Standard
Sigma-Aldrich
cis-Diamineplatinum(II) dichloride, ≥99.9% trace metals basis