West LA Times

Selecting specific cells for investigational therapy led to improved heart function recovery in a new study using a lab model for myocardial infarction, the medical term for heart attacks. Researchers at the California NanoSystems Institute at UCLA and Columbia University developed a sorting method grouping stem cells based on their vesicle release involved in cellular communication. Treatment with high-secreting cells restored heart function to a state similar to pre-myocardial infarction damage.

Numerous treatments under development use cells as delivery devices for therapeutic molecules or as therapies themselves. Some use mesenchymal stem cells (MSCs), found in fat tissue or bone marrow, aiming to heal damaged heart muscle post-myocardial infarction by delivering extracellular vesicles, which are naturally occurring cell secretions.

Extracellular vesicles facilitate cellular communication, composed of waxy, protein-laden membranes carrying DNA and RNA instructions. They often reduce inflammation or promote healing and are hypothesized to deliver more information than smaller signaling proteins or hormones.

Although MSC-delivered vesicles have shown effectiveness in regenerating heart tissue in preclinical research, replicating this success in patient studies has been challenging. This difficulty may be due to varying rates of vesicle production among MSCs from different patients or tissues. Currently, no known markers predict which MSCs will secrete more vesicles, nor are there methods to sort cells based on this function.

The team sorted MSCs using nanovials—microscopic hydrogel containers developed by CNSI researchers. These nanovials were decorated with proteins and antibodies that MSCs and vesicles latch onto, enabling individual cell capture and filtering based on vesicle release using standard lab instruments.

High-secreting MSCs grown in culture for two weeks maintained high production rates and grew faster than low-secreting MSCs. Gene expression analysis revealed higher activation levels of genes related to regeneration and blood vessel growth in high-secreting cells.

In a lab model, heart tissue treated with high-secreting stem cells showed more regeneration compared to tissue treated with low-secreting cells or receiving no treatment.

Two groups of mice treated with high- and low-secreting MSCs post-myocardial infarction showed increased heart function measures after 28 days, while the control group showed a decrease. Notably, those treated with high-secreting cells reached levels approaching baseline before heart damage.

This study suggests isolating and growing MSCs that release more vesicles can lead to better outcomes after a heart attack. It also indicates that other cell-based treatments could be more effective if nanovials select for higher therapeutic secretion production. Sorting high-secreting cells may enhance the efficiency of manufacturing cell-derived medicines in labs.

The study’s corresponding authors are Dino Di Carlo from UCLA Samueli School of Engineering and Ke Cheng from Columbia University. Co-first authors include Doyeon Koo from UCLA and Xiao Cheng from UNC Chapel Hill/North Carolina State University. Other co-authors come from various institutions including Xsome Biotech, Cytek Biosciences, and the University of Pennsylvania.

Di Carlo and the University of California have financial interests in Partillion Bioscience commercializing nanovial technology. The study was published in Nature Communications and supported by NIH, AHA, and Chan Zuckerberg Initiative.