Protective Effects of Human Liver Stem Cell-Derived Extracellular Vesicles in a Mouse Model of Hepatic Ischemia-Reperfusion Injury
Hepatic ischemia-reperfusion injury (IRI) is observed in liver transplantation and hepato-biliary surgery and is associated with an inflammatory response. Human liver stem cell-derived extracellular vesicles (HLSC-EV) have been demonstrated to reduce liver damage in different experimental settings by accelerating regeneration and by modulating inflammation. The aim of the present study was to investigate whether HLSC-EV may protect liver from IRI in a mouse experimental model. Segmental IRI was obtained by selective clamping of intrahepatic pedicles for 90 min followed by 6 h of reperfusion. HLSC-EV were administered intravenously at the end of the ischemic period and histopathological and biochemical alterations were evaluated in comparison with controls injected with vehicle alone. Intra liver localization of labeled HLSC-EV was assessed by in in vivo Imaging System (IVIS) and the internalization into hepatocytes was confirmed by fluorescence analyses. As compared to the control group, administration of 3 × 109 particles (EV1 group) significantly reduced alanine aminotransferase (ALT) and lactate dehydrogenase (LDH) release, necrosis extension and cytokines expression (TNF-α, CCL-2 and CXCL-10). However, the administration of an increased dose of HLSC-EV (7.5 × 109 particles, EV2 group) showed no significant improvement in respect to controls at enzyme and histology levels, despite a significantly lower cytokine expression. In conclusion, this study demonstrated that 3 × 109 HLSC-EV were able to modulate hepatic IRI by preserving tissue integrity and by reducing transaminases release and inflammatory cytokines expression. By contrast, a higher dose was ineffective suggesting a restricted window of biological activity. Graphical abstract.
Medienart: |
E-Artikel |
---|
Erscheinungsjahr: |
2021 |
---|---|
Erschienen: |
2021 |
Enthalten in: |
Zur Gesamtaufnahme - volume:17 |
---|---|
Enthalten in: |
Stem cell reviews and reports - 17(2021), 2 vom: 04. Apr., Seite 459-470 |
Sprache: |
Englisch |
---|
Beteiligte Personen: |
Calleri, Alberto [VerfasserIn] |
---|
Links: |
---|
Themen: |
Adult stem cells |
---|
Anmerkungen: |
Date Completed 03.03.2022 Date Revised 03.03.2022 published: Print-Electronic Citation Status MEDLINE |
---|
doi: |
10.1007/s12015-020-10078-7 |
---|
funding: |
|
---|---|
Förderinstitution / Projekttitel: |
|
PPN (Katalog-ID): |
NLM318355795 |
---|
LEADER | 01000naa a22002652 4500 | ||
---|---|---|---|
001 | NLM318355795 | ||
003 | DE-627 | ||
005 | 20231225165202.0 | ||
007 | cr uuu---uuuuu | ||
008 | 231225s2021 xx |||||o 00| ||eng c | ||
024 | 7 | |a 10.1007/s12015-020-10078-7 |2 doi | |
028 | 5 | 2 | |a pubmed24n1061.xml |
035 | |a (DE-627)NLM318355795 | ||
035 | |a (NLM)33269415 | ||
040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
041 | |a eng | ||
100 | 1 | |a Calleri, Alberto |e verfasserin |4 aut | |
245 | 1 | 0 | |a Protective Effects of Human Liver Stem Cell-Derived Extracellular Vesicles in a Mouse Model of Hepatic Ischemia-Reperfusion Injury |
264 | 1 | |c 2021 | |
336 | |a Text |b txt |2 rdacontent | ||
337 | |a ƒaComputermedien |b c |2 rdamedia | ||
338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
500 | |a Date Completed 03.03.2022 | ||
500 | |a Date Revised 03.03.2022 | ||
500 | |a published: Print-Electronic | ||
500 | |a Citation Status MEDLINE | ||
520 | |a Hepatic ischemia-reperfusion injury (IRI) is observed in liver transplantation and hepato-biliary surgery and is associated with an inflammatory response. Human liver stem cell-derived extracellular vesicles (HLSC-EV) have been demonstrated to reduce liver damage in different experimental settings by accelerating regeneration and by modulating inflammation. The aim of the present study was to investigate whether HLSC-EV may protect liver from IRI in a mouse experimental model. Segmental IRI was obtained by selective clamping of intrahepatic pedicles for 90 min followed by 6 h of reperfusion. HLSC-EV were administered intravenously at the end of the ischemic period and histopathological and biochemical alterations were evaluated in comparison with controls injected with vehicle alone. Intra liver localization of labeled HLSC-EV was assessed by in in vivo Imaging System (IVIS) and the internalization into hepatocytes was confirmed by fluorescence analyses. As compared to the control group, administration of 3 × 109 particles (EV1 group) significantly reduced alanine aminotransferase (ALT) and lactate dehydrogenase (LDH) release, necrosis extension and cytokines expression (TNF-α, CCL-2 and CXCL-10). However, the administration of an increased dose of HLSC-EV (7.5 × 109 particles, EV2 group) showed no significant improvement in respect to controls at enzyme and histology levels, despite a significantly lower cytokine expression. In conclusion, this study demonstrated that 3 × 109 HLSC-EV were able to modulate hepatic IRI by preserving tissue integrity and by reducing transaminases release and inflammatory cytokines expression. By contrast, a higher dose was ineffective suggesting a restricted window of biological activity. Graphical abstract | ||
650 | 4 | |a Journal Article | |
650 | 4 | |a Research Support, Non-U.S. Gov't | |
650 | 4 | |a Adult stem cells | |
650 | 4 | |a Hepatic inflammation | |
650 | 4 | |a Ischemia-reperfusion | |
650 | 4 | |a Liver regeneration | |
650 | 4 | |a Microvesicles | |
650 | 7 | |a Cytokines |2 NLM | |
700 | 1 | |a Roggio, Dorotea |e verfasserin |4 aut | |
700 | 1 | |a Navarro-Tableros, Victor |e verfasserin |4 aut | |
700 | 1 | |a De Stefano, Nicola |e verfasserin |4 aut | |
700 | 1 | |a Pasquino, Chiara |e verfasserin |4 aut | |
700 | 1 | |a David, Ezio |e verfasserin |4 aut | |
700 | 1 | |a Frigatti, Giada |e verfasserin |4 aut | |
700 | 1 | |a Rigo, Federica |e verfasserin |4 aut | |
700 | 1 | |a Antico, Federica |e verfasserin |4 aut | |
700 | 1 | |a Caropreso, Paola |e verfasserin |4 aut | |
700 | 1 | |a Patrono, Damiano |e verfasserin |4 aut | |
700 | 1 | |a Bruno, Stefania |e verfasserin |4 aut | |
700 | 1 | |a Romagnoli, Renato |e verfasserin |4 aut | |
773 | 0 | 8 | |i Enthalten in |t Stem cell reviews and reports |d 2009 |g 17(2021), 2 vom: 04. Apr., Seite 459-470 |w (DE-627)NLM18490143X |x 2629-3277 |7 nnns |
773 | 1 | 8 | |g volume:17 |g year:2021 |g number:2 |g day:04 |g month:04 |g pages:459-470 |
856 | 4 | 0 | |u http://dx.doi.org/10.1007/s12015-020-10078-7 |3 Volltext |
912 | |a GBV_USEFLAG_A | ||
912 | |a GBV_NLM | ||
951 | |a AR | ||
952 | |d 17 |j 2021 |e 2 |b 04 |c 04 |h 459-470 |