Abstract 18886: A Universal Secretory Signature

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Abstract

Paracrine signaling by transplanted stem cells can be an important mediator of their therapeutic effects at the sites of acute or persistent injury and inflammation. Understanding the molecular signature and nature of stem cell secretion would facilitate development of cell-less therapy for cardiac repair. Secretory signature, representing the composition, dosage, and kinetics of secreted factors, is an outcome of integration of extracellular stimuli, relaying these signals to other responsive cells. However, precise measurement of dynamic and context-specific cellular secretory signatures, particularly in adherent cells, remains challenging. We created a high throughput platform combining protein microprinting and microfluidics designed to directly measure cellular secretion in adherent and non-adherent cells subject to arbitrary in-chip pre-conditioning. The platform, in combination with a new computational algorithm, can be used to precisely estimate dynamic secretory signatures based on a very limited number of time points. Using this platform we compared the secretory language of a variety of stem cell types that have been used in clinical trials to treat myocardial infarction. We found that secretion of stem cells are uniquely defined by distinct biological contexts, including signals from cardiac cells undergoing oxidative stress, characteristic of cardiac infarction. Furthermore, many stem cell types with reported benefits secrete a similar minimal cocktail which, when reconstituted using recombinant proteins, can provide significant cardioprotection against oxidative stress. We are currently testing this minimal common cocktail from various stem cell types improve cardiac function in a rat model of myocardial infarction and reperfusion similar to stem cell themselves. These results pave a way for stem cell-inspired cell-less treatments of cardiac injuries and other syndromes.

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