Development of a new therapeutic technique to direct stem cells to the infarcted heart using targeted microbubbles: StemBells

• Published in: Stem cell research Vol. 17; no. 1; pp. 6 - 15
• Main Authors: Woudstra, L., Krijnen, P.A.J., Bogaards, S.J.P., Meinster, E., Emmens, R.W., Kokhuis, T.J.A., Bollen, I.A.E., Baltzer, H., Baart, S.M.T., Parbhudayal, R., Helder, M.N., van Hinsbergh, V.W.M., Musters, R.J.P., de Jong, N., Kamp, O., Niessen, H.W.M., van Dijk, A., Juffermans, L.J.M.
• Format: Journal Article
• Language: English
• Published: England Elsevier B.V 01.07.2016; Elsevier
• Subjects: Acoustic radiation force; Acute myocardial infarction; Adipose Tissue - cytology; Adipose Tissue - metabolism; Adipose tissue-derived stem cells; Administration, Intravenous; Animals; Antigens, CD - metabolism; Antigens, Differentiation, Myelomonocytic - metabolism; Cell Survival; Cells, Cultured; Disease Models, Animal; Echocardiography; Heart - diagnostic imaging; Heart - physiopathology; Humans; Macrophages - metabolism; Macrophages - pathology; Male; Microbubbles; Myocardial Infarction - metabolism; Myocardial Infarction - pathology; Myocardial Infarction - therapy; Pilot Projects; Rats; Rats, Wistar; Sonication; Stem Cell Transplantation - methods; Stem Cells - cytology; Stem Cells - metabolism; StemBells; Targeting; Microbubbles; StemBells; Targeting; Acute myocardial infarction; Adipose tissue-derived stem cells; Acoustic radiation force
• ISSN: 1873-5061; 1876-7753
• DOI: 10.1016/j.scr.2016.04.018

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. •Novel technique to target stem cells in vivo•StemBells: adipose stem cells coupled to microbubbles with targeted antibodies conjugated to the microbubble shell•StemBells are subjective to acoustic radiation force and safely administered intravenously in rats•Treatment of acute myocardial infarction with StemBells results in improved cardiac function•StemBells bear the perspective to be applicable in a variety of diseases that may require regenerative cellular therapy