Intramyocardial fate and effect of iron nanoparticles co-injected with MACS® purified stem cell products

Paula Müller; Ralf Gaebel; Heiko Lemcke; Frank Wiekhorst; Frauke Hausburg; Cajetan Lang; Nicole Zarniko; Bernd Westphal; Gustav Steinhoff; Robert David

doi:10.1016/j.biomaterials.2017.05.002

Intramyocardial fate and effect of iron nanoparticles co-injected with MACS^® purified stem cell products

Biomaterials. 2017 Aug:135:74-84. doi: 10.1016/j.biomaterials.2017.05.002. Epub 2017 May 4.

Authors

Affiliations

¹ Reference and Translation Center for Cardiac Stem Cell Therapy (RTC), Department of Cardiac Surgery, Rostock University Medical Center, Schillingallee 69, 18057 Rostock, Germany; Department Life, Light and Matter of the Interdisciplinary Faculty at Rostock University, Albert-Einstein Straße 25, 18059 Rostock, Germany. Electronic address: paula.mueller@uni-rostock.de.
² Reference and Translation Center for Cardiac Stem Cell Therapy (RTC), Department of Cardiac Surgery, Rostock University Medical Center, Schillingallee 69, 18057 Rostock, Germany; Department Life, Light and Matter of the Interdisciplinary Faculty at Rostock University, Albert-Einstein Straße 25, 18059 Rostock, Germany. Electronic address: ralf.gaebel@uni-rostock.de.
³ Reference and Translation Center for Cardiac Stem Cell Therapy (RTC), Department of Cardiac Surgery, Rostock University Medical Center, Schillingallee 69, 18057 Rostock, Germany; Department Life, Light and Matter of the Interdisciplinary Faculty at Rostock University, Albert-Einstein Straße 25, 18059 Rostock, Germany. Electronic address: heiko.lemcke@uni-rostock.de.
⁴ Physikalisch-Technische Bundesanstalt (PTB), Abbestraße 2-12, 10587 Berlin, Germany. Electronic address: frank.wiekhorst@ptb.de.
⁵ Reference and Translation Center for Cardiac Stem Cell Therapy (RTC), Department of Cardiac Surgery, Rostock University Medical Center, Schillingallee 69, 18057 Rostock, Germany; Department Life, Light and Matter of the Interdisciplinary Faculty at Rostock University, Albert-Einstein Straße 25, 18059 Rostock, Germany. Electronic address: frauke.hausburg@uni-rostock.de.
⁶ Reference and Translation Center for Cardiac Stem Cell Therapy (RTC), Department of Cardiac Surgery, Rostock University Medical Center, Schillingallee 69, 18057 Rostock, Germany; Department of Cardiology, Rostock University Medical Center, Ernst-Heydemann-Straße 6, 18057 Rostock, Germany. Electronic address: cajetan.lang@med.uni-rostock.de.
⁷ Reference and Translation Center for Cardiac Stem Cell Therapy (RTC), Department of Cardiac Surgery, Rostock University Medical Center, Schillingallee 69, 18057 Rostock, Germany. Electronic address: n.zarniko@uke.de.
⁸ Department of Cardiac Surgery, Rostock University Medical Center, Schillingallee 35, 18057 Rostock, Germany. Electronic address: bernd.westphal@med.uni-rostock.de.
⁹ Reference and Translation Center for Cardiac Stem Cell Therapy (RTC), Department of Cardiac Surgery, Rostock University Medical Center, Schillingallee 69, 18057 Rostock, Germany; Department Life, Light and Matter of the Interdisciplinary Faculty at Rostock University, Albert-Einstein Straße 25, 18059 Rostock, Germany. Electronic address: gustav.steinhoff@med.uni-rostock.de.
¹⁰ Reference and Translation Center for Cardiac Stem Cell Therapy (RTC), Department of Cardiac Surgery, Rostock University Medical Center, Schillingallee 69, 18057 Rostock, Germany; Department Life, Light and Matter of the Interdisciplinary Faculty at Rostock University, Albert-Einstein Straße 25, 18059 Rostock, Germany. Electronic address: robert.david@med.uni-rostock.de.

PMID: 28494265
DOI: 10.1016/j.biomaterials.2017.05.002

Abstract

Background: Magnetic activated cell sorting (MACS^®) is routinely used to isolate stem cell subpopulations intended for the treatment of cardiovascular diseases. In strong contrast, studies examining the amount, effect and intramyocardial distribution of iron nanoparticles used for magnetic cell labelling are missing, although iron excess can cause functional disorders in the heart.

Methods and results: CD133⁺ haematopoietic and CD271⁺ mesenchymal stem cells were purified from bone marrow using automatically and manually MACS^® based systems. Flow cytometric measurements demonstrated a rapid loss of MACS^® MicroBeads from cells under culture conditions, while storage under hypothermic conditions decelerated their detachment. Moreover, an average loading of ∼11 fg iron/cell caused by magnetic labelling was determined in magnetic particle spectroscopy. Importantly, hemodynamic measurements as well as histological examinations using a myocardial ischemia/reperfusion mouse model showed no influence of MACS^® MicroBeads on cardiac regeneration, while the transplantation of stem cells caused a significant improvement. Furthermore, immunostainings demonstrated the clearance of co-injected iron nanoparticles from stem cells and the surrounding heart tissue within 48 h post transplantation.

Conclusions: Our results indicate that iron amounts typically co-injected with MACS^® purified stem cells do not harm cardiac functions and are cleared from heart tissue within a few hours. Therefore, we conclude that MACS^® MicroBeads exhibit a good compatibility in the cardiac environment.

Keywords: Cardiovascular regeneration; Haematopoietic stem cells (HSCs); MACS(®) MicroBeads; Magnetic activated cell sorting (MACS(®)); Mesenchymal stem cells (MSCs); Stem cell therapy.

MeSH terms

AC133 Antigen / metabolism
Adapalene / metabolism
Animals
Cell Survival / physiology
Cells, Cultured
Flow Cytometry
Hematopoietic Stem Cells / cytology
Hematopoietic Stem Cells / metabolism*
Humans
Iron / chemistry
Iron / metabolism*
Leukocytes, Mononuclear / metabolism
Mesenchymal Stem Cells / cytology
Mesenchymal Stem Cells / metabolism
Mice, SCID
Myocardium / cytology
Myocardium / metabolism*
Nanoparticles / chemistry
Nanoparticles / metabolism*

Substances

AC133 Antigen
Adapalene
Iron