Title
Development of a new therapeutic technique to direct stem cells to the infarcted heart using targeted microbubbles: StemBells
Author
Woudstra, L. (Amsterdam UMC)
Krijnen, PAJ (Amsterdam UMC)
Bogaards, SJP (Amsterdam UMC)
Meinster, E (Amsterdam UMC)
Emmens, RW (Amsterdam UMC; Erasmus MC)
Kokhuis, TJA (Interuniversity Cardiology Institute of the Netherlands (ICIN))
Bollen, IAE (Amsterdam UMC)
Baltzer, H (Amsterdam UMC)
Baart, SMT (Amsterdam UMC)
Parbhudayal, R (Amsterdam UMC)
de Jong, N. (TU Delft ImPhys/Acoustical Wavefield Imaging; Erasmus MC; Interuniversity Cardiology Institute of the Netherlands (ICIN))
Helder, MN (Amsterdam UMC)
Hinsbergh, V.W.M. (Amsterdam UMC)
Musters, RJP (Amsterdam UMC)
Kamp, O. (Interuniversity Cardiology Institute of the Netherlands (ICIN); Amsterdam UMC)
Niessen, H.W.M. (Amsterdam UMC)
van Dijk, A. (Amsterdam UMC)
Juffermans, LJ (Amsterdam UMC; Interuniversity Cardiology Institute of the Netherlands (ICIN))
Date
2016
Abstract
Successful stem cell therapy after acute myocardial infarction (AMI) is hindered by lack of engraftment of sufficient stem cells at the site of injury. We designed a novel technique to overcome this problem by assembling stem cell-microbubble complexes, named 'StemBells'. StemBells were assembled through binding of dual-targeted microbubbles (~3μm) to adipose-derived stem cells (ASCs) via a CD90 antibody. StemBells were targeted to the infarct area via an ICAM-1 antibody on the microbubbles. StemBells were characterized microscopically and by flow cytometry. The effect of ultrasound on directing StemBells towards the vessel wall was demonstrated in an in vitro flow model. In a rat AMI-reperfusion model, StemBells or ASCs were injected one week post-infarction. A pilot study demonstrated feasibility of intravenous StemBell injection, resulting in localization in ICAM-1-positive infarct area three hours post-injection. In a functional study five weeks after injection of StemBells cardiac function was significantly improved compared with controls, as monitored by 2D-echocardiography. This functional improvement neither coincided with a reduction in infarct size as determined by histochemical analysis, nor with a change in anti- and pro-inflammatory macrophages. In conclusion, the StemBell technique is a novel and feasible method, able to improve cardiac function post-AMI in rats.
Subject
Acoustic radiation force
Acute myocardial infarction
Adipose tissue-derived stem cells
Microbubbles
StemBells
Targeting
To reference this document use:
http://resolver.tudelft.nl/uuid:31bce0f8-c532-4264-8caf-155f4eda537d
DOI
https://doi.org/10.1016/j.scr.2016.04.018
Source
Stem Cell Research, 17 (1), 6-15
Part of collection
Institutional Repository
Document type
journal article
Rights
© 2016 L. Woudstra, PAJ Krijnen, SJP Bogaards, E Meinster, RW Emmens, TJA Kokhuis, IAE Bollen, H Baltzer, SMT Baart, R Parbhudayal, N. de Jong, MN Helder, V.W.M. Hinsbergh, RJP Musters, O. Kamp, H.W.M. Niessen, A. van Dijk, LJ Juffermans