Zivko, C. | bioRxiv Science

bioRxiv2025

Magnetically Labeled iPSC-Derived Extracellular Vesicles Enable MRI/MPI-Guided Regenerative Therapy for Myocardial Infarction

Stem cell-derived extracellular vesicles (EVs) offer a promising cell-free approach for cardiovascular regenerative medicine. In this study, we developed magnetically labeled induced pluripotent stem cell-derived EVs (magneto-iPSC-EVs) encapsulated with superparamagnetic iron oxide (SPIO) nanoparticles for image-guided regenerative treatment of myocardial infarction, in which EVs that can be detected by both magnetic resonance imaging (MRI) and magnetic particle imaging (MPI). iPSC-EVs were isolated, characterized per MISEV2023 guidelines, and loaded with SuperSPIO20 nanoparticles using optimized electroporation conditions (300 V, 2 x 10 ms pulses), achieving a high loading efficiency of 1.77 ng Fe/106 EVs. In vitro results show that magneto-iPSC-EVs can be sensitively detected by MPI and MRI, with a detectability of approximately 107 EVs. In a mouse myocardial ischemia-reperfusion model, intramyocardially injected magneto-iPSC-EVs (2 x 109) were imaged non-invasively by in vivo MPI for 7 days and ex vivo MRI, with the presence of magneto-iPSC-EVs confirmed by Prussian blue staining. Therapeutically, both native and magneto-iPSC-EVs significantly improved cardiac function, with a 37.3% increase in left ventricular ejection fraction and 61.0% reduction in scar size. This study highlights the potential of magneto-iPSC-EVs as a cell-free approach for cardiovascular regenerative medicine, offering both non-invasive imaging capabilities and therapeutic benefits for myocardial repair.

bioengineering↗

bioRxiv2023

Excitatory neurons derived from human induced Pluripotent Stem Cells show transcriptomic differences in Alzheimers patients from controls

The recent advances in creating pluripotent stem cells from somatic cells and differentiating them into a variety of cell types is allowing us to study them without the caveats associated with disease related changes. We have generated induced Pluripotent Stem Cells (iPSCs) from eight Alzheimers disease (AD) patients and six controls and used lentiviral delivery to differentiate them into excitatory glutamatergic neurons. We have performed RNA sequencing on these neurons and compared the Alzheimers and control transcriptomes. We find that 621 genes show differences in expression levels at adjusted p<0.05 between the case and control derived neurons. These genes show significant overlap and direction concordance with genes reported from a Single cell transcriptome study of Alzheimers patients, they contain 5 genes implicated with AD from genome wide association studies and they appear to be part of a larger functional network as indicated by an excess of interactions between them observed in the protein-protein interaction database STRING. Exploratory analysis with Uniform Manifold Approximation and Projection (UMAP) suggests distinct clusters of patients, based on gene expression, who maybe clinically different. If confirmed this finding will to contribute to precision medicine approaches to subgroup Alzheimers disease.

genetics↗