Icon Legend

This session is not in your schedule.

This session is in your schedule. Click again to remove it.

Cellular and Molecular Bioengineering

Cellular and Molecular Bioengineering - Poster Session E

Poster U14 - Chromatin Reprogramming for Cardiovascular Regenerative Engineering

Saturday, October 26, 2024

10:00 AM – 11:00 AM EST

Location: Exhibit Hall E, F & G

Presenting Author(s)

NR

Nancy Rivera-Bolanos, Ms

Graduate Student
Northwestern University
Evanston, Illinois, United States

Co-Author(s)

CD

Cody Dunton

PostDoc
Northwestern University BME, United States
Vadim Backman, PhD

McCormick School of Engineering Professor
Northwestern University BME, United States

Primary Investigator(s)

GA

Guillermo Ameer

Daniel Hale Williams Professor of Biomedical Engineering, McCormick School of Engineering Professor
1 Department of Biomedical Engineering, Northwestern University, 2 Center for Advanced Regenerative Engineering (CARE), 3 Department of Surgery, Northwestern University Feinberg School of Medicine, United States

Introduction: Cardiovascular disease is the primary cause of death in the United States, with a myocardial infarct occurring every 40 seconds. Occlusion of the vessel leads to hypoxia and low nutrient levels in the surrounding cardiac tissue. This results in tissue inflammation, cardiomyocyte necrosis, and cardiac fibroblast activation leading to ventricular scaring and diminished cardiovascular function. Low frequency electromagnetic fields (LFEMF) can reprogram cellular functions in cardiac cells, including cell proliferation and differentiation, DNA synthesis, and transcription. This study examines the effects LFEMF has on cardiac cell reprogramming to determine whether it is a viable treatment option for cardiac pathology following an infarction.

Materials and

Methods: Primary human cardiac fibroblasts (hCFBs) and human cardiomyocyte cell line (AC16) were cultured in standard culture media. Media was then replaced with low nutrient media and exposed to 5% O2 hypoxic conditions via a custom hypoxia chamber housed in an incubator. After cells displayed a response to hypoxic conditions, LFEMF was applied to cells via a SyntheXer® system. Various stimulation parameters were investigated, including frequency (Hz), power (mW), and duration (minutes). After stimulation, the effect of LFEMF on cell behavior, chromatin reprogramming, and nuclear ion flux were investigated via phenotypic assays, nano-imaging, and ion labeling, respectively.

Results, Conclusions, and Discussions: Cardiomyocytes and fibroblasts displayed a differential response to LFEMF. When compared with cells exposed to hypoxia, cardiomyocytes demonstrated increased chromatin packing scaling (D) indicative of increased transcriptional plasticity, sustained cell proliferation, increased nuclear area, and increased nuclear [Ca2+] upon stimulation with 100 Hz at 150 mW for 60 minutes. Contrary to the cardiomyocyte response, fibroblasts demonstrated a decrease in D, reduced cell proliferation, and no change in nuclear area upon stimulation with 200 Hz at 150 mW for 60 minutes. 48 hours after a single stimulation, neither cardiomyocytes nor fibroblasts exhibited sustained changes in D. This study suggests that cardiomyocytes and fibroblasts respond to LFEMF in a differential manner consistent with cell reprogramming for cardiovascular therapeutics. Cardiomyocytes have an increased ability to adapt and survive in an ischemic environment by enhancing the transcriptional plasticity of genes involved in cell survival. Alternatively, treatment of fibroblasts with LFEMF decreased transcriptional malleability and proliferation, indicating that scar formation may be diminished. The outcome of this study suggests that LFEMF may be a viable non-invasive treatment option following a myocardial infarct.

Acknowledgements (Optional):