Biology subjects

Weiss, R. G.

Publications and source records attributed to Weiss, R. G..

4 recordsLinked to original sources

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↗

bioRxiv2024

Mitochondrial Oxidative Phosphorylation Capacity in Skeletal Muscle Measured by Ultrafast Z-Spectroscopy (UFZ) MRI at 3T

BackgroundTo investigate the feasibility of rapid CEST MRI acquisition for evaluating oxidative phosphorylation (OXPHOS) in human skeletal muscle at 3 Tesla, utilizing ultrafast Z-spectroscopy (UFZ) MRI combined with the Polynomial and Lorentzian line-shape Fitting (PLOF) technique. MethodsUFZ MRI on muscle was evaluated with turbo spin echo (TSE) and segmented 3D EPI readouts. Five healthy subjects performed in-magnet plantar flexion exercise (PFE) and subsequent changes of amide, phosphocreatine (PCr) and partial PCr mixed creatine (Cr+) CEST dynamic signals post-exercise were enabled by PLOF fitting. PCr/Cr CEST signal was further refined through pH correction by using the ratios between PCr/Cr and amide signals, named PCAR/CAR, respectively. ResultsUFZ MRI with TSE readout significantly reduces acquisition time, achieving a temporal resolution of <50 seconds for collecting high-resolution Z-spectra. Following PFE, the recovery/decay times ({tau}) for both PCr and Cr in the gastrocnemius muscle of the calf were notably longer when determined using PCr/Cr CEST compared to those after pH correction with amideCEST, namely [Formula] s and{tau} PCr = 98.1 {+/-} 20.4 s versus{tau} CAR =36.4 {+/-} 18.6 s and{tau} PCAR = 43.0 {+/-} 13.0 s, respectively. Literature values of{tau} PCr obtained via 31P MRS closely resemble those obtained from pH-corrected PCr/Cr CEST signals. ConclusionThe outcomes suggest potential of UFZ MRI as a robust tool for non-invasive assessment of mitochondrial function in skeletal muscles. pH correction is critical for the reliable OXPHOS measurement by CEST.

biophysics↗

bioRxiv2020

Mitochondrial CaMKII causes metabolic reprogramming, energetic insufficiency, and dilated cardiomyopathy

Despite the clear association between myocardial injury, heart failure and depressed myocardial energetics, little is known about upstream signals responsible for remodeling myocardial metabolism after pathological stress. We found increased mitochondrial calmodulin kinase II (CaMKII) activation and left ventricular dilation in mice one week after myocardial infarction (MI) surgery. In contrast, mice with genetic mitochondrial CaMKII inhibition were protected from left ventricular dilation and dysfunction after MI. Mice with myocardial and mitochondrial CaMKII over-expression (mtCaMKII) had severe dilated cardiomyopathy and decreased ATP that caused elevated cytoplasmic resting (diastolic) Ca2+ concentration and reduced mechanical performance. We mapped a metabolic pathway that allowed us to rescue disease phenotypes in mtCaMKII mice, providing new insights into physiological and pathological metabolic consequences of CaMKII signaling in mitochondria. Our findings suggest myocardial dilation, a disease phenotype lacking specific therapies, can be prevented by targeted replacement of mitochondrial creatine kinase, or mitochondrial-targeted CaMKII inhibition.

molecular biology↗

bioRxiv2019

MRI tracking reveals selective accumulation of stem cell-derived magneto-extracellular vesicles in sites of injury

Human stem-cell-derived extracellular vesicles (EVs) are currently being investigated for cell-free therapy in regenerative medicine applications, but their biodistribution and tropic properties for homing to injured tissues are largely unknown. Here, we labeled EVs with magnetic nanoparticles to create magneto-EVs that can be tracked by magnetic resonance imaging (MRI). Superparamagnetic iron oxide (SPIO) nanoparticles were coated with polyhistidine tags, which enabled purification of labeled EVs by efficiently removing unencapsulated SPIO particles in the solution. The biodistribution of systemically injected human induced pluripotent stem cell (iPSC)-derived magneto-EV was assessed in three different animal models of kidney injury and myocardial ischemia. Magneto-EVs were found to selectively home to the injury sites and conferred substantial protection in a kidney injury model. In vivo MRI tracking of magnetically labeled EVs represents a new powerful method to assess and quantify their whole-body distribution, which may help optimize further development of EV-based cell-free therapy.

bioengineering↗