TY - JOUR
T1 - Cardiac recovery via extended cell-free delivery of extracellular vesicles secreted by cardiomyocytes derived from induced pluripotent stem cells
AU - Liu, Bohao
AU - Lee, Benjamin W.
AU - Nakanishi, Koki
AU - Villasante, Aranzazu
AU - Williamson, Rebecca
AU - Metz, Jordan
AU - Kim, Jinho
AU - Kanai, Mariko
AU - Bi, Lynn
AU - Brown, Kristy
AU - Di Paolo, Gilbert
AU - Homma, Shunichi
AU - Sims, Peter A.
AU - Topkara, Veli K.
AU - Vunjak-Novakovic, Gordana
N1 - Publisher Copyright:
© 2018 The Author(s) 2018, under exclusive licence to Macmillan Publishers Ltd, part of Springer Nature.
PY - 2018/5/1
Y1 - 2018/5/1
N2 - 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.
AB - 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.
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U2 - 10.1038/s41551-018-0229-7
DO - 10.1038/s41551-018-0229-7
M3 - Article
AN - SCOPUS:85045841910
VL - 2
SP - 293
EP - 303
JO - Nature Biomedical Engineering
JF - Nature Biomedical Engineering
IS - 5
ER -