Human heart explant-derived extracellular vesicles: Characterization and effects on the in vitro recellularization of decellularized heart valves

Amanda Leitolis; Paula Hansen Suss; João Gabriel Roderjan; Addeli Bez Batti Angulski; Francisco Diniz Affonso da Costa; Marco Augusto Stimamiglio; Alejandro Correa

doi:10.3390/ijms20061279

Human heart explant-derived extracellular vesicles: Characterization and effects on the in vitro recellularization of decellularized heart valves

Amanda Leitolis, Paula Hansen Suss, João Gabriel Roderjan, Addeli Bez Batti Angulski, Francisco Diniz Affonso da Costa, Marco Augusto Stimamiglio, Alejandro Correa

Physiology

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13 Scopus citations

Abstract

Extracellular vesicles (EVs) are particles released from different cell types and represent key components of paracrine secretion. Accumulating evidence supports the beneficial effects of EVs for tissue regeneration. In this study, discarded human heart tissues were used to isolate human heart-derived extracellular vesicles (hH-EVs). We used nanoparticle tracking analysis (NTA) and transmission electron microscopy (TEM) to physically characterize hH-EVs and mass spectrometry (MS) to profile the protein content in these particles. The MS analysis identified a total of 1248 proteins. Gene ontology (GO) enrichment analysis in hH-EVs revealed the proteins involved in processes, such as the regulation of cell death and response to wounding. The potential of hH-EVs to induce proliferation, adhesion, angiogenesis and wound healing was investigated in vitro. Our findings demonstrate that hH-EVs have the potential to induce proliferation and angiogenesis in endothelial cells, improve wound healing and reduce mesenchymal stem-cell adhesion. Last, we showed that hH-EVs were able to significantly promote mesenchymal stem-cell recellularization of decellularized porcine heart valve leaflets. Altogether our data confirmed that hH-EVs modulate cellular processes, shedding light on the potential of these particles for tissue regeneration and for scaffold recellularization.

Original language	English (US)
Article number	1279
Journal	International journal of molecular sciences
Volume	20
Issue number	6
DOIs	https://doi.org/10.3390/ijms20061279
State	Published - Mar 2 2019

Bibliographical note

Funding Information:
This study was supported by the National Health Fund, Brazilian Ministry of Health (Grant number 814611/2014) and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior, Brasil (CAPES)–Finance Code 001. Acknowledgments: The authors thank the staff of Carlos Chagas Institute (Fiocruz-PR) for laboratory and administrative support and the staff of the Homograft Bank (Human Tissue Bank—PUCPR) for tissue collection. We would like to thank the Program for Technological Development in Tools for Health-PDTIS-FIOCRUZ for the use of the flow cytometry core facility, mass spectrometry facility and microscopy facility.

Funding Information:
Funding: This study was supported by the National Health Fund, Brazilian Ministry of Health (Grant number 814611/2014) and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior, Brasil (CAPES)–Finance Code 001.

Publisher Copyright:
© 2019 by the authors. Licensee MDPI, Basel, Switzerland.

Keywords

Cardiac regions
Extracellular vesicle
Heart valve
Human heart
Mesenchymal stromal cells
Recellularization
Tissue engineering
Tissue explant

Publisher link

10.3390/ijms20061279

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Leitolis, A., Suss, P. H., Roderjan, J. G., Angulski, A. B. B., da Costa, F. D. A., Stimamiglio, M. A., & Correa, A. (2019). Human heart explant-derived extracellular vesicles: Characterization and effects on the in vitro recellularization of decellularized heart valves. International journal of molecular sciences, 20(6), Article 1279. https://doi.org/10.3390/ijms20061279

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title = "Human heart explant-derived extracellular vesicles: Characterization and effects on the in vitro recellularization of decellularized heart valves",

abstract = "Extracellular vesicles (EVs) are particles released from different cell types and represent key components of paracrine secretion. Accumulating evidence supports the beneficial effects of EVs for tissue regeneration. In this study, discarded human heart tissues were used to isolate human heart-derived extracellular vesicles (hH-EVs). We used nanoparticle tracking analysis (NTA) and transmission electron microscopy (TEM) to physically characterize hH-EVs and mass spectrometry (MS) to profile the protein content in these particles. The MS analysis identified a total of 1248 proteins. Gene ontology (GO) enrichment analysis in hH-EVs revealed the proteins involved in processes, such as the regulation of cell death and response to wounding. The potential of hH-EVs to induce proliferation, adhesion, angiogenesis and wound healing was investigated in vitro. Our findings demonstrate that hH-EVs have the potential to induce proliferation and angiogenesis in endothelial cells, improve wound healing and reduce mesenchymal stem-cell adhesion. Last, we showed that hH-EVs were able to significantly promote mesenchymal stem-cell recellularization of decellularized porcine heart valve leaflets. Altogether our data confirmed that hH-EVs modulate cellular processes, shedding light on the potential of these particles for tissue regeneration and for scaffold recellularization.",

keywords = "Cardiac regions, Extracellular vesicle, Heart valve, Human heart, Mesenchymal stromal cells, Recellularization, Tissue engineering, Tissue explant",

author = "Amanda Leitolis and Suss, {Paula Hansen} and Roderjan, {Jo{\~a}o Gabriel} and Angulski, {Addeli Bez Batti} and {da Costa}, {Francisco Diniz Affonso} and Stimamiglio, {Marco Augusto} and Alejandro Correa",

note = "Funding Information: This study was supported by the National Health Fund, Brazilian Ministry of Health (Grant number 814611/2014) and Coordena{\c c}{\~a}o de Aperfei{\c c}oamento de Pessoal de N{\'i}vel Superior, Brasil (CAPES)–Finance Code 001. Acknowledgments: The authors thank the staff of Carlos Chagas Institute (Fiocruz-PR) for laboratory and administrative support and the staff of the Homograft Bank (Human Tissue Bank—PUCPR) for tissue collection. We would like to thank the Program for Technological Development in Tools for Health-PDTIS-FIOCRUZ for the use of the flow cytometry core facility, mass spectrometry facility and microscopy facility. Funding Information: Funding: This study was supported by the National Health Fund, Brazilian Ministry of Health (Grant number 814611/2014) and Coordena{\c c}{\~a}o de Aperfei{\c c}oamento de Pessoal de N{\'i}vel Superior, Brasil (CAPES)–Finance Code 001. Publisher Copyright: {\textcopyright} 2019 by the authors. Licensee MDPI, Basel, Switzerland.",

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AU - Angulski, Addeli Bez Batti

AU - da Costa, Francisco Diniz Affonso

AU - Stimamiglio, Marco Augusto

AU - Correa, Alejandro

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N2 - Extracellular vesicles (EVs) are particles released from different cell types and represent key components of paracrine secretion. Accumulating evidence supports the beneficial effects of EVs for tissue regeneration. In this study, discarded human heart tissues were used to isolate human heart-derived extracellular vesicles (hH-EVs). We used nanoparticle tracking analysis (NTA) and transmission electron microscopy (TEM) to physically characterize hH-EVs and mass spectrometry (MS) to profile the protein content in these particles. The MS analysis identified a total of 1248 proteins. Gene ontology (GO) enrichment analysis in hH-EVs revealed the proteins involved in processes, such as the regulation of cell death and response to wounding. The potential of hH-EVs to induce proliferation, adhesion, angiogenesis and wound healing was investigated in vitro. Our findings demonstrate that hH-EVs have the potential to induce proliferation and angiogenesis in endothelial cells, improve wound healing and reduce mesenchymal stem-cell adhesion. Last, we showed that hH-EVs were able to significantly promote mesenchymal stem-cell recellularization of decellularized porcine heart valve leaflets. Altogether our data confirmed that hH-EVs modulate cellular processes, shedding light on the potential of these particles for tissue regeneration and for scaffold recellularization.

AB - Extracellular vesicles (EVs) are particles released from different cell types and represent key components of paracrine secretion. Accumulating evidence supports the beneficial effects of EVs for tissue regeneration. In this study, discarded human heart tissues were used to isolate human heart-derived extracellular vesicles (hH-EVs). We used nanoparticle tracking analysis (NTA) and transmission electron microscopy (TEM) to physically characterize hH-EVs and mass spectrometry (MS) to profile the protein content in these particles. The MS analysis identified a total of 1248 proteins. Gene ontology (GO) enrichment analysis in hH-EVs revealed the proteins involved in processes, such as the regulation of cell death and response to wounding. The potential of hH-EVs to induce proliferation, adhesion, angiogenesis and wound healing was investigated in vitro. Our findings demonstrate that hH-EVs have the potential to induce proliferation and angiogenesis in endothelial cells, improve wound healing and reduce mesenchymal stem-cell adhesion. Last, we showed that hH-EVs were able to significantly promote mesenchymal stem-cell recellularization of decellularized porcine heart valve leaflets. Altogether our data confirmed that hH-EVs modulate cellular processes, shedding light on the potential of these particles for tissue regeneration and for scaffold recellularization.

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KW - Extracellular vesicle

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KW - Human heart

KW - Mesenchymal stromal cells

KW - Recellularization

KW - Tissue engineering

KW - Tissue explant

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Human heart explant-derived extracellular vesicles: Characterization and effects on the in vitro recellularization of decellularized heart valves

Abstract

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Keywords

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