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

Müller, Paula; Gaebel, Ralf; Lemcke, Heiko; Wiekhorst, Frank; Hausburg, Frauke; Lang, Cajetan Immanuel; Zarniko, Nicole; Westphal, Bernd; Steinhoff, Gustav; Dávid, Róbert

doi:10.1016/j.biomaterials.2017.05.002

Cited by 25 publications

(20 citation statements)

References 90 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…CD133 + and CD271 + cells were automatically and manually isolated as previously described [1], [3].…”

Section: Experimental Design Materials and Methodsmentioning

confidence: 99%

“…The data presented in this article are related to the research article “Intramyocardial Fate and Effect of Iron Nanoparticles co-injected with MACS® purified Stem Cell Products” (Müller et al, 2017) [1]. This article complements the cellular localization of superparamagnetic iron dextran particles (MACS® MicroBeads) used for magnetic activated cell sorting (MACS®).…”

mentioning

confidence: 99%

See 1 more Smart Citation

Data on the fate of MACS® MicroBeads intramyocardially co-injected with stem cell products

et al. 2017

Self Cite

View full text Add to dashboard Cite

The data presented in this article are related to the research article “Intramyocardial Fate and Effect of Iron Nanoparticles co-injected with MACS® purified Stem Cell Products” (Müller et al., 2017) [1]. This article complements the cellular localization of superparamagnetic iron dextran particles (MACS® MicroBeads) used for magnetic activated cell sorting (MACS®). Data evaluate the time-dependent detachment of these nanoparticles from CD133+ haematopoietic stem cells (HSCs) and CD271+ mesenchymal stem cells (MSCs). Furthermore, the influence of these stem cells as well as of nanoparticles on cardiac remodeling processes after myocardial infarction (MI) was investigated.

show abstract

“…CD133 + and CD271 + cells were automatically and manually isolated as previously described [1], [3].…”

Section: Experimental Design Materials and Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

Data on the fate of MACS® MicroBeads intramyocardially co-injected with stem cell products

et al. 2017

Self Cite

View full text Add to dashboard Cite

show abstract

“…Injections of 4 × 5 µL were given along the infarct border. The injection site was controlled visually at the time of transplantation [10].…”

Section: Animal Modelmentioning

confidence: 99%

18F-FDG PET-Based Imaging of Myocardial Inflammation Predicts a Functional Outcome Following Transplantation of mESC-Derived Cardiac Induced Cells in a Mouse Model of Myocardial Infarction

Vasudevan

Gaebel

Doering

et al. 2019

Cells

Self Cite

View full text Add to dashboard Cite

Cellular inflammation following acute myocardial infarction has gained increasing importance as a target mechanism for therapeutic approaches. We sought to investigate the effect of syngeneic cardiac induced cells (CiC) on myocardial inflammation using 18F-FDG PET (Positron emission tomography)-based imaging and the resulting effect on cardiac pump function using cardiac magnetic resonance (CMR) imaging in a mouse model of myocardial infarction. Mice underwent permanent left anterior descending coronary artery (LAD) ligation inducing an acute inflammatory response. The therapy group received an intramyocardial injection of 10 6 CiC into the border zone of the infarction. Five days after myocardial infarction, 18F-FDG PET was performed under anaesthesia with ketamine and xylazine (KX) to image the inflammatory response in the heart. Flow cytometry of the mononuclear cells in the heart was performed to analyze the inflammatory response. The effect of CiC therapy on cardiac function was determined after three weeks by CMR. The 18F-FDG PET imaging of the heart five days after myocardial infarction (MI) revealed high focal tracer accumulation in the border zone of the infarcted myocardium, whereas no difference was observed in the tracer uptake between infarct and remote myocardium. The CiC transplantation induced a shift in 18F-FDG uptake pattern, leading to significantly higher 18F-FDG uptake in the whole heart, as well as the remote area of the heart. Correspondingly, high numbers of CD11 + cells could be measured by flow cytometry in this region. The CiC transplantation significantly improved the left ventricular ejection function (LVEF) three weeks after myocardial infarction. The CiC transplantation after myocardial infarction leads to an improvement in pump function through modulation of the cellular inflammatory response five days after myocardial infarction. By combining CiC transplantation and the cardiac glucose uptake suppression protocol with KX in a mouse model, we show for the first time, that imaging of cellular inflammation after myocardial infarction using 18F-FDG PET can be used as an early prognostic tool for assessing the efficacy of cardiac stem cell therapies.

show abstract

“…Some have been defined as pro-arrhythmogenic cells, i.e., skeletal myoblasts, while others have shown antiarrhythmic effects, such as embryonic cardiomyocytes and mesenchymal stem cells (MSC) [2][3][4][5]. Our research group has focused on the role of human bone marrow (BM) derived hematopoiesis such as MSC in regenerative medicine [6][7][8][9]. In previous studies we have shown that it is safe to use CD117 + stem cells for myocardial regeneration, as their electrophysiological properties…”

Section: Introductionmentioning

confidence: 99%

CD271+ Human Mesenchymal Stem Cells Show Antiarrhythmic Effects in a Novel Murine Infarction Model

Sadraddin

Gaebel

Skorska

et al. 2019

Cells

Self Cite

View full text Add to dashboard Cite

Background: Ventricular arrhythmias (VA) are a common cause of sudden death after myocardial infarction (MI). Therefore, developing new therapeutic methods for the prevention and treatment of VA is of prime importance. Methods: Human bone marrow derived CD271 + mesenchymal stem cells (MSC) were tested for their antiarrhythmic effect. This was done through the development of a novel mouse model using an immunocompromised Rag2 −/− γc −/− mouse strain subjected to myocardial "infarction-reinfarction". The mice underwent a first ischemia-reperfusion through the left anterior descending (LAD) artery closure for 45 min with a subsequent second permanent LAD ligation after seven days from the first infarct. Results: This mouse model induced various types of VA detected with continuous electrocardiogram (ECG) monitoring via implanted telemetry device. The immediate intramyocardial delivery of CD271 + MSC after the first MI significantly reduced VA induced after the second MI. Conclusions: In addition to the clinical relevance, more closely reflecting patients who suffer from severe ischemic heart disease and related arrhythmias, our new mouse model bearing reinfarction warrants the time required for stem cell engraftment and for the first time enables us to analyze and verify significant antiarrhythmic effects of human CD271 + stem cells in vivo. make them very unlikely to produce hazardous action potentials or contribute to arrhythmias [10,11]. However, the availability of a realistic small animal model reflecting the situation in patients is of utmost importance. For testing the rhythmological behavior of human cells, Rag2 −/− γc −/− has been selected. These mice (strain C, 129S4-Rag2 tm1.1Flv Il2rg tm1.1Flv /J) have been derived from a V17 embryonic stem cell line (BALB/c × 129 heterozygote) targeted for the Rag2 and Il2rg genes and lack B, T, and natural killer (NK) cells [12]. They have a deletion of the common cytokine receptor γ chain (γc) gene, and thus reduced numbers of peripheral T and B lymphocytes, and absent natural killer cell (NK) activity. A genetic cross with a recombinase activating gene 2 (RAG2) deficient strain produced mice doubly homozygous for the γc and RAG2 null alleles (Rag2 −/− γc −/− ) with a stable phenotype characterized by the absence of all T lymphocyte, B lymphocyte, and NK cell function [13]. This phenotype makes the completely a lymphoid strain useful for studies on human tissue xenotransplantation [14].As previously shown, stem cell antiarrhythmic effects appear after completion of an approximately one-week engraftment period [4]. The major objective of the present study was to develop a mouse model that enables us to reproduce VA several days after an initial MI. In vivo electrophysiological mouse models are well established: Previously, Berul et al. established an open chest epicardial study of conduction properties with the ability to induce second and third degree heart blocks, but no induction of tachyarrhythmias after programmed stimulation [15]. Hagendorff et al. used a rapid t...

show abstract

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

Cited by 25 publications

References 90 publications

Data on the fate of MACS® MicroBeads intramyocardially co-injected with stem cell products

Data on the fate of MACS® MicroBeads intramyocardially co-injected with stem cell products

18F-FDG PET-Based Imaging of Myocardial Inflammation Predicts a Functional Outcome Following Transplantation of mESC-Derived Cardiac Induced Cells in a Mouse Model of Myocardial Infarction

CD271+ Human Mesenchymal Stem Cells Show Antiarrhythmic Effects in a Novel Murine Infarction Model

Contact Info

Product

Resources

About