Targeted delivery of bone mesenchymal stem cells by ultrasound destruction of microbubbles promotes kidney recovery in acute kidney injury

Ultrasound Med Biol. 2012 Apr;38(4):661-9. doi: 10.1016/j.ultrasmedbio.2012.01.003.

Abstract

The aim of the present study was to explore whether ultrasound microbubble destruction augments site-targeted engraftment of bone marrow mesenchymal stem cells (BM-MSCs) to kidney tissue and promotes recovery of the kidney in acute kidney injury (AKI) in rats. AKI was induced by the subcutaneous injection of mercuric chloride (HgCl₂). Forty Sprague-Dawley (SD) rats were randomly divided into the following groups after the establishment of rat models of AKI (n = 10): (1) Model group alone (control group); (2) 1.0 W/cm² ultrasound (US) + microbubble (MB) (US/MB group); (3) MSCs group; and (4) 1.0 W/cm² US+MB + MSCs group (US/MB + MSCs group). The number of 4',6-diamidino-2-phenylindole (DAPI) labelled MSCs was evaluated by fluorescence microscopy and real-time polymerase chain reaction (RT-PCR) and Western blotting and histological examination were performed 7 days after MSCs transplantation. It was observed via fluorescence microscopy that the number of DAPI-labelled MSCs in the kidney for the US/MB + MSCs group was significantly more than the MSCs group (p < 0.05). The results from RT-PCR revealed that the US/MB and US/MB + MSCs groups markedly increased the level of inter-cellular adhesion molecule 1 (ICAM-1) messenger ribonucleic acid (mRNA) compared with the control group and the MSCs group (p < 0.05). Western blot analysis showed that the expression of hepatocyte growth factor (HGF) and epidermal growth factor (EGF) in the US/MB + MSCs group were markedly increased compared with the all other groups (p < 0.01). The extent of tubular necrosis and dilation was significantly milder in the US/MB + MSCs group (acoustic exposure conditions: 5s at 1 MHz and 1.0 W/cm² with a 5s pause, totalling 60 s) than the all other groups (p < 0.05). Microbubble destruction by 1.0 W/cm² ultrasound can promote both the homing of BM-MSCs to kidney tissue and the recovery of the kidney in AKI in rats.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Kidney Injury / diagnostic imaging
  • Acute Kidney Injury / metabolism
  • Acute Kidney Injury / therapy*
  • Analysis of Variance
  • Animals
  • Blotting, Western
  • Disease Models, Animal
  • Indoles
  • Intercellular Adhesion Molecule-1 / metabolism
  • Microbubbles
  • Microscopy, Fluorescence
  • Phenotype
  • Random Allocation
  • Rats
  • Rats, Sprague-Dawley
  • Real-Time Polymerase Chain Reaction
  • Ultrasonics*
  • Ultrasonography

Substances

  • Indoles
  • Intercellular Adhesion Molecule-1
  • DAPI