Cardiac recovery via extended cell-free delivery of extracellular vesicles secreted by cardiomyocytes derived from induced pluripotent stem cells

Bohao Liu, Benjamin W. Lee, Koki Nakanishi, Aranzazu Villasante, Rebecca Williamson, Jordan Metz, Jinho Kim, Mariko Kanai, Lynn Bi, Kristy Brown, Gilbert Di Paolo, Shunichi Homma, Peter A. Sims, Veli K. Topkara, Gordana Vunjak-Novakovic

Research output: Contribution to journalArticlepeer-review

275 Scopus citations

Abstract

The ability of extracellular vesicles (EVs) to regulate a broad range of cellular processes has recently been exploited for the treatment of diseases. For example, EVs secreted by therapeutic cells injected into infarcted hearts can induce recovery through the delivery of cell-specific microRNAs. However, retention of the EVs and the therapeutic effects are short-lived. Here, we show that an engineered hydrogel patch capable of slowly releasing EVs secreted from cardiomyocytes (CMs) derived from induced pluripotent stem cells reduced arrhythmic burden, promoted ejection-fraction recovery, decreased CM apoptosis 24 h after infarction, and reduced infarct size and cell hypertrophy 4 weeks post-infarction when implanted onto infarcted rat hearts. We also show that EVs are enriched with cardiac-specific microRNAs known to modulate CM-specific processes. The extended delivery of EVs secreted from induced-pluripotent-stem-cell-derived CMs into the heart may help us to treat heart injury and to understand heart recovery.

Original languageEnglish
Pages (from-to)293-303
Number of pages11
JournalNature Biomedical Engineering
Volume2
Issue number5
DOIs
StatePublished - 1 May 2018

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