Exosomes and beyond: translation of small molecules and cellular organelles
Pharmacologic therapies have improved survival in heart failure (HF) patients over the past three decades. Despite these pioneering medical therapies, HF is the leading diagnosis of hospital admission associated with high morbidity and mortality. This public health epidemic highlights the need for a development of innovative treatment strategies. Heart failure represents bioenergetic imbalance. The disruption of this cellular balance between energy supply and demand underlies the pathogenesis of HF.
Recent evidence indicates that the stem cells exert their therapeutic action via paracrine mechanisms through microvesicles, which show distinct functionalities in tissue self-repair and -maintenance. These microvesicles ranging from 40 to 400 nm in diameter are formed by endosomal membrane and released into the extracellular space. They contain unique cytoplasmic small molecules, proteins, and cellular organelles that function as intercellular messengers and effectors, controlling a wide spectrum of genetic regulation. Our data demonstrated that the miR cluster and mitochondria contained within these microvesicles underlie the mechanism of action of iPSC-derivatives in repairing the injured and vulnerable heart. These microvesicles have therapeutic potential to protect all the cells in the human body against early death, inflammation, hypertrophy, fibrosis, and energy demand. Our data provide unique insights into the potential of endogenous microvesicles generated from the autologous iPSC-derivatives for personalized, precision medicine. This approach, employing a person’s rejuvenated cellular components and molecules from iPSCs, may underlie a novel strategy to address HF.
Phillip C. Yang is an Associate Professor of Medicine (Cardiovascular Medicine) at the Stanford University School of Medicine. He directs the Cardiovascular Stem Cell Laboratory (Yang Lab) and Stanford Cardiovascular MRI Program. Dr. Yang received degrees from Stanford University and Yale University School of Medicine.
Dr. Yang is a physician-scientist whose research focuses on cardiovascular regeneration. His laboratory combines stem cell biology with novel imaging technology to advance clinical implementation of induced pluripotent stem cells and their derivatives. Regenerative medicine will trigger a paradigm shift and his research provides a requisite validation for clinical translation. Dr. Yang is a Principal Investigator of the National Institute of Health (NIH) funded Cardiovascular Cell Therapy Research Network designed to conduct multi-center clinical trial on novel stem cell therapy. In addition, he leads multiple NIH, foundation, and pharmaceutical research grants along with five clinical trials. He has received several prestigious awards, including the NIH Career Development Award, NIH Career Enhancement Award in Stem Cell Biology, NIH Mid-career Award, and multiple awards from both the American Heart Association and American College of Cardiology. He is a frequent guest speaker and session chair at national and international meetings.