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UID:998@biotech.technion.ac.il
DTSTART;TZID=Asia/Jerusalem:20210119T173000
DTEND;TZID=Asia/Jerusalem:20220202T164952
DTSTAMP:20220512T124719Z
URL:https://biotech.technion.ac.il/events/advanced-technologies-for-regene
 rative-medicine-2/
SUMMARY:Advanced Technologies for Regenerative Medicine
DESCRIPTION:Ischemic heart disease (IHD) is a leading cause of death worldw
 ide. Current treatments help with managing symptoms of the disease. Howeve
 r\, the damaged myocardial tissue remains unfunctional\, leading to progre
 ssion of the disease to heart failure. Therefore\, minimizing infarct size
  and salvaging the infarcted myocardium is crucial for preventing heart fa
 ilure in IHD patients. Extracellular vesicles (EVs) derived from various s
 tem cell sources induce cardioprotective effects during ischemia-reperfusi
 on injury (IRI). These have been attributed mainly to the anti-apoptotic\,
  pro-angiogenic\, miRNA cargo within the stem cell derived EVs. However\, 
 endothelial cells\, which are naturally abundant in the heart and are sens
 itive to oxygen deprivation\, may hold therapeutic potential toward ischem
 ic myocardial injury via EV-mediated signaling. To test this\, human endot
 helial EVs (EEVs) were isolated and characterized. To assess their human-s
 pecific cardioprotection in vitro\, we developed a human heart-on-a-chip (
 hHOC) IRI assay using human stem cell-derived\, engineered cardiac tissues
 . EEVs alleviated cardiac cell death as well as the loss in contractile ca
 pacity during and after simulated IRI\, in an uptake- and dose-dependent m
 anner. Moreover\, EEVs increased the respiratory capacity of cardiomyocyte
 s. To further understand the EEV-mediated cardio-protection their effects 
 on cardiomyocytes proteome was investigated. EEVs partially restored prote
 in profiles of the injured myocytes towards healthy profiles\, while prese
 nting enrichment of various metabolic processes related to cellular respir
 ation and modulation of the cellular response to stress. EEV protein cargo
  was characterized and lead cardioactive proteins were identified. Specifi
 cally\, EEVs contained proteins that were previously associated with cellu
 lar metabolism\, redox state\, and calcium handling\, among other processe
 s\, corresponding with the modifications EEVs induced to the myocytes’ p
 roteome. These results suggest that vascular EEVs rescue human cardiac tis
 sues exposed to IRI possibly by supplementing injured myocytes with cargo 
 that supports multiple metabolic and salvage pathways\, and therefore may 
 serve as a multi-targeted therapy for IRI. Since the cellular manifestatio
 ns of IRI are not unique to cardiomyocyte\, and are generally common to va
 rious cell types\, EEVs may provide similar protection against IRI in othe
 r organ tissues. In the future\, deeper understanding of their mechanisms 
 of action will enable engineering of EEV mimetics that are optimized for t
 reating IRI in different clinical scenarios.\n\nFull Abstract
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