Heart on a chip

Promising new therapies for heart attacks identified

Thursday 15 Oct 20
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Johan Ulrik Lind
Groupleader, Assistant Professor
DTU Health Tech

Researchers from Harvard University and DTU Health Tech have discovered that tiny vesicles travelling between cells provide protection against heart attacks

Heart attacks occur when blood supply to the heart is blocked and the tissue is deprived of oxygen and nutrients. Remarkably, further damage often occurs upon restoration of blood flow, in what is collectively known as ischemia-reperfusion injury (IRI).

 

Now, in a paper presented in Science Translational Medicine, researchers have found that extracellular vesicles released by the endothelial cells — the cells that line the interior of the blood vessels — can serve as new therapy against IRI. Extracellular vesicles can be described as nanosized containers that travel between cells to deliver cues and cargo. Surprisingly, it turns out that endothelial extracellular vesicles can counteract cell death and help the heart muscle sustain its function during a heart attack. The researchers were able to show this using an instrumented heart-on-a-chip, in which embedded sensors continuously tracked the contractions of the human cardiac muscle tissue.

 

The researchers were further able to show that the vesicles carry a diverse cargo that may can protect against ischemia-reperfusion injury through several distinct mechanisms. Findings that point towards exciting unexplored therapeutic possibilities.

“When we analyzed the cargo of the vesicles, we found a multitude of proteins that relate to metabolic processes like respiration, mitochondrial function, signaling and homeostasis. Along with the RNA content, these proteins appear to play a key role in the improved response to ischemic stress we observed for the cardiac tissue”, says Research Scientist Moran Yadid, first author of the study.

 

Such a multi-target approach stands in contrast to traditional therapies, senior author Professor Kevin Kit Parker, Harvard University, explains: "Exosomal cell therapies, might be indicated where the traditional model of one molecule-one target just won't cure the disease. With an exosome, or the vesicles we administered, we believe we are taking a shotgun approach to hitting a network of drug targets.”

 

Assistant Professor Johan Ulrik Lind from DTU Health Tech, who is the second author of the paper, has developed the heart-on-a-chip technology used in the study. He highlights the exciting potential for accelerating and improving drug development. “One of the fundamental challenges in developing new therapies, and cell-derived therapies in particular, is the species differences between animal models and human patients. By replicating a heart attack in a heart-on-a-chip format, we were able to test our hypothesis directly on human tissue. Interestingly, when we reformulated the heart-on-a-chip assay to be based on heart cells from a rat, the effects were much less pronounced.” 

 

Read the original research published in Science Translational Medicinehere
Read the news article from Harvard here

 

Picture caption: The embedded sensor in the heart-on-a-chip bends to track the contractions of the heart tissue



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https://www.cmr.healthtech.dtu.dk/news/Nyhed?id=%7BE46D7AA1-21ED-4567-AEDC-4FB75E6FB615%7D
30 NOVEMBER 2020