Heart cells speak a common language with different accents

By Adrienne Mueller, PhD
November 3, 2020

Cells communicate with each other in many different ways, one of which is the release of small vesicle packets called exosomes. Exosomes are filled with tiny molecules such as microRNA, a very short, regulatory form of RNA. The collection of molecules released by secreted exosomes can influence nearby cells’ behavior, function, development, and even identity. Exosomes are therefore a way for cells to communicate with each other. What CVI-affiliated co-first authors Mark Chandy, MD, PhD, June-Wha Rhee, MD and Mehmet Ozen, PhD and co-senior authors Edward Lau, PhD, Utkan Demirci, PhD and Joseph C. Wu, MD, PhD wanted to find out is what different types of heart cells are saying to each other via exosomes.

The investigators used human induced pluripotent stem cells to create three different lineages of heart cells: heart muscle cells (cardiomyocytes), endothelial cells, and fibroblasts. They then went on to collect the exosomes from these three different cell types using a unique tool developed in Stanford, ExoTIC, and compared their microRNA contents. As they report in their recent paper in Circulation, the exosomes of these three different cells possess a shared set of microRNAs, but each cell also releases a specific subset of microRNAs that the other cell types do not. For example, heart muscle cells are the only cells that secrete microRNA-1, which is critical for cardiac development. This study therefore found that microRNAs from different heart cell exosomes reflect a common set of information, but also have distinct characteristics unique to the different cell types.

Two additional benefits that stem from this study. First, the authors were able to create an interactive atlas of exosomal microRNAs that allows anyone to explore the relative abundance of particular microRNAs in different tissues. Second, their experiments determined that exosome content scales with cell number—so researchers can read out exosome content to report how many cells of the different cell types are present in their stem cell preparations. Being able to determine the abundance of different cell types will be extremely useful for measuring the purity of cardiac cell preparations, which is important for regenerative medicine, disease modeling and drug screening. As Dr. Chandy and Dr. Rhee describe, “Working collaboratively in the Wu, Demirci, and Lau laboratories, we have created an interactive exosomal microRNA atlas of different cardiac lineages that has application in stem cell biology, regenerative medicine and disease biomarker discovery.”

Other Stanford Cardiovascular Institute-affiliated authors include Damon R. Williams, Lejla Pepic, Chun Liu, Hao Zhang, and Jessica Malisa.