Related Experiment Video
Updated: Jul 14, 2025
Flow Cytometric Analysis of Extracellular Vesicles from Cell-conditioned Media
Published on: February 12, 2019
Engineered Extracellular Vesicle-Based Therapies for Valvular Heart Disease
Ana I Salazar-Puerta1, Mia Kordowski2, Tatiana Z Cuellar-Gaviria1
1Department of Biomedical Engineering, The Ohio State University, Fontana Laboratories, 140 W. 19th Ave., Columbus, OH 43210 USA.
Insights
Engineered extracellular vesicles (EVs) deliver reprogramming factors to calcified aortic valves, successfully inducing anti-inflammatory macrophage-like cells. This novel nanocarrier approach offers a promising therapy for heart valve disease.
Area of Science:
- Cardiovascular Research
- Nanomedicine
- Regenerative Medicine
Background:
- Valvular heart disease, particularly calcific aortic stenosis (CAS), is a major health concern in aging populations.
- Current treatments like valve replacement have limitations in long-term durability.
- Novel strategies are needed to halt or reverse CAS progression.
Purpose of the Study:
- To explore the potential of extracellular vesicles (EVs) as nanocarriers for delivering therapeutic payloads to diseased aortic valves.
- To investigate the use of engineered EVs loaded with specific transcription factors to reduce inflammation and promote calcified tissue resorption.
Main Methods:
- Engineered EVs were loaded with reprogramming myeloid transcription factors, CEBPA and Spi1.
- The ability of these EVs to deliver genetic material and induce cell transdifferentiation was evaluated in patient-derived aortic valve tissue.
- In vitro and ex vivo models were used to assess the induction of macrophage-like cells from endothelial cells.
Main Results:
- Engineered EVs loaded with CEBPA and Spi1 were successfully derived from human dermal fibroblasts.
- These EVs effectively transfected aortic valve cells, inducing the transdifferentiation of endothelial cells into anti-inflammatory macrophage-like cells.
- Successful transdifferentiation was observed both in vitro and ex vivo.
Conclusions:
- Engineered EVs show potential as a next-generation nanocarrier for targeting aberrant calcifications in heart valves.
- This approach may offer a novel therapeutic option for high-risk patients unsuitable for valve replacement surgery.
Introduction:
Valvular heart disease represents a significant burden to the healthcare system, with approximately 5 million cases diagnosed annually in the US. Among these cases, calcific aortic stenosis (CAS) stands out as the most prevalent form of valvular heart disease in the aging population. CAS is characterized by the progressive calcification of the aortic valve leaflets, leading to valve stiffening. While aortic valve replacement is the standard of care for CAS patients, the long-term durability of prosthetic devices is poor, calling for innovative strategies to halt or reverse disease progression. Here, we explor the potential use of novel extracellular vesicle (EV)-based nanocarriers for delivering molecular payloads to the affected valve tissue. This approach aims to reduce inflammation and potentially promote resorption of the calcified tissue.
Methods:
Engineered EVs loaded with the reprogramming myeloid transcription factors, CEBPA and Spi1, known to mediate the transdifferentiation of committed endothelial cells into macrophages. We evaluated the ability of these engineered EVs to deliver DNA and transcripts encoding CEBPA and Spil into calcified aortic valve tissue obtained from patients undergoing valve replacement due to aortic stenosis. We also investigated whether these EVs could induce the transdifferentiation of endothelial cells into macrophage-like cells.
Results:
Engineered EVs loaded with CEBPA + Spi1 were successfully derived from human dermal fibroblasts. Peak EV loading was found to be at 4 h after nanotransfection of donor cells. These CEBPA + Spi1 loaded EVs effectively transfected aortic valve cells, resulting in the successful induction of transdifferentiation, both in vitro with endothelial cells and ex vivo with valvular endothelial cells, leading to the development of anti-inflammatory macrophage-like cells.
Conclusions:
Our findings highlight the potential of engineered EVs as a next generation nanocarrier to target aberrant calcifications on diseased heart valves. This development holds promise as a novel therapy for high-risk patients who may not be suitable candidates for valve replacement surgery.
Supplementary Information:
The online version contains supplementary material available at 10.1007/s12195-023-00783-x.
More Related Videos
Related Concept Videos
01:22Heart Failure VI: Adjunct Therapies
01:16Heart Valves
The AV valves prevent the backflow of blood from the ventricles to the atria during ventricular contraction. These valves function with the assistance of the chordae tendineae and papillary muscles. When the ventricles are relaxed, the chordae tendineae are slack, allowing blood to flow from the atria into the...
01:29Cardiomyopathy V: Interprofessional Care
01:30Heart Failure V: Medical Management