Intravital microscopy of localized stem cell delivery using microbubbles and acoustic radiation force

T.J.A. Kokhuis*, I. Skachkov, B.A. Naaijkens, L.J.M. Juffermans, O. Kamp, K. Kooiman, A.F.W. van der Steen, M. Versluis, N. de Jong

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

34 Citations (Scopus)


The use of stem cells for the repair of damaged cardiac tissue after a myocardial infarction holds great promise. However, a common finding in experimental studies is the low number of cells delivered at the area at risk. To improve the delivery, we are currently investigating a novel delivery platform in which stem cells are conjugated with targeted microbubbles, creating echogenic complexes dubbed StemBells. These StemBells vibrate in response to incoming ultrasound waves making them susceptible to acoustic radiation force. The acoustic force can then be employed to propel circulating StemBells from the centerline of the vessel to the wall, facilitating localized stem cell delivery. In this study, we investigate the feasibility of manipulating StemBells acoustically in vivo after injection using a chicken embryo model. Bare stem cells or unsaturated stem cells (<5bubbles/cell) do not respond to ultrasound application (1MHz, peak negative acoustical pressure P_=200kPa, 10% duty cycle). However, stem cells which are fully saturated with targeted microbubbles (>30bubbles/cell) can be propelled toward and arrested at the vessel wall. The mean translational velocities measured are 61 and 177μm/s for P-=200 and 450kPa, respectively. This technique therefore offers potential for enhanced and well-controlled stem cell delivery for improved cardiac repair after a myocardial infarction.

Original languageEnglish
Pages (from-to)220-227
Number of pages8
JournalBiotechnology and bioengineering
Issue number1
Publication statusPublished - 1 Jan 2015


  • Acoustic radiation force
  • Mesenchymal stem cell
  • Microbubble
  • Stem cell delivery
  • StemBell
  • Ultrasound
  • 2023 OA procedure

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