Protein and Molecular Characterization of a Clinically Compliant Amniotic Fluid Stem Cell-Derived Extracellular Vesicle Fraction Capable of Accelerating Muscle Regeneration Through Enhancement of Angiogenesis

Ben Mellows, Robert Mitchell, Manuela Antonioli, Oliver Kretz, David Chambers, Marie Theres Zeuner, Bernd Denecke, Luca Musante, Durrgah L. Ramachandra, Florence Debacq-Chainiaux, Harry Holthofer, Barbara Joch, Steve Ray, Darius Widera, Anna L. David, Tobias B. Huber, Joern Dengjel, Paolo De Coppi, Ketan Patel

Résultats de recherche: Contribution à un journal/une revueArticle

Résumé

The secretome of human amniotic fluid stem cells (AFSCs) has great potential as a therapeutic agent in regenerative medicine. However, it must be produced in a clinically compliant manner before it can be used in humans. In this study, we developed a means of producing a biologically active secretome from AFSCs that is free of all exogenous molecules. We demonstrate that the full secretome is capable of promoting stem cell proliferation, migration, and protection of cells against senescence. Furthermore, it has significant anti-inflammatory properties. Most importantly, we show that it promotes tissue regeneration in a model of muscle damage. We then demonstrate that the secretome contains extracellular vesicles (EVs) that harbor much, but not all, of the biological activity of the whole secretome. Proteomic characterization of the EV and free secretome fraction shows the presence of numerous molecules specific to each fraction that could be key regulators of tissue regeneration. Intriguingly, we show that the EVs only contain miRNA and not mRNA. This suggests that tissue regeneration in the host is mediated by the action of EVs modifying existing, rather than imposing new, signaling pathways. The EVs harbor significant anti-inflammatory activity as well as promote angiogenesis, the latter may be the mechanistic explanation for their ability to promote muscle regeneration after cardiotoxin injury.

langueAnglais
Pages1316-1333
Nombre de pages18
journalStem Cells and Development
Volume26
Numéro18
Les DOIs
étatPublié - 15 sept. 2017

Empreinte digitale

Amniotic Fluid
Regeneration
Stem Cells
Muscles
Proteins
Anti-Inflammatory Agents
Cardiotoxins
Regenerative Medicine
Cytoprotection
Cell Aging
MicroRNAs
Proteomics
Cell Movement
Cell Proliferation
Extracellular Vesicles
Messenger RNA
Wounds and Injuries

mots-clés

    Citer ceci

    Mellows, Ben ; Mitchell, Robert ; Antonioli, Manuela ; Kretz, Oliver ; Chambers, David ; Zeuner, Marie Theres ; Denecke, Bernd ; Musante, Luca ; Ramachandra, Durrgah L. ; Debacq-Chainiaux, Florence ; Holthofer, Harry ; Joch, Barbara ; Ray, Steve ; Widera, Darius ; David, Anna L. ; Huber, Tobias B. ; Dengjel, Joern ; De Coppi, Paolo ; Patel, Ketan. / Protein and Molecular Characterization of a Clinically Compliant Amniotic Fluid Stem Cell-Derived Extracellular Vesicle Fraction Capable of Accelerating Muscle Regeneration Through Enhancement of Angiogenesis. Dans: Stem Cells and Development. 2017 ; Vol 26, Numéro 18. p. 1316-1333
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    abstract = "The secretome of human amniotic fluid stem cells (AFSCs) has great potential as a therapeutic agent in regenerative medicine. However, it must be produced in a clinically compliant manner before it can be used in humans. In this study, we developed a means of producing a biologically active secretome from AFSCs that is free of all exogenous molecules. We demonstrate that the full secretome is capable of promoting stem cell proliferation, migration, and protection of cells against senescence. Furthermore, it has significant anti-inflammatory properties. Most importantly, we show that it promotes tissue regeneration in a model of muscle damage. We then demonstrate that the secretome contains extracellular vesicles (EVs) that harbor much, but not all, of the biological activity of the whole secretome. Proteomic characterization of the EV and free secretome fraction shows the presence of numerous molecules specific to each fraction that could be key regulators of tissue regeneration. Intriguingly, we show that the EVs only contain miRNA and not mRNA. This suggests that tissue regeneration in the host is mediated by the action of EVs modifying existing, rather than imposing new, signaling pathways. The EVs harbor significant anti-inflammatory activity as well as promote angiogenesis, the latter may be the mechanistic explanation for their ability to promote muscle regeneration after cardiotoxin injury.",
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    author = "Ben Mellows and Robert Mitchell and Manuela Antonioli and Oliver Kretz and David Chambers and Zeuner, {Marie Theres} and Bernd Denecke and Luca Musante and Ramachandra, {Durrgah L.} and Florence Debacq-Chainiaux and Harry Holthofer and Barbara Joch and Steve Ray and Darius Widera and David, {Anna L.} and Huber, {Tobias B.} and Joern Dengjel and {De Coppi}, Paolo and Ketan Patel",
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    Mellows, B, Mitchell, R, Antonioli, M, Kretz, O, Chambers, D, Zeuner, MT, Denecke, B, Musante, L, Ramachandra, DL, Debacq-Chainiaux, F, Holthofer, H, Joch, B, Ray, S, Widera, D, David, AL, Huber, TB, Dengjel, J, De Coppi, P & Patel, K 2017, 'Protein and Molecular Characterization of a Clinically Compliant Amniotic Fluid Stem Cell-Derived Extracellular Vesicle Fraction Capable of Accelerating Muscle Regeneration Through Enhancement of Angiogenesis' Stem Cells and Development, VOL. 26, Numéro 18, p. 1316-1333. DOI: 10.1089/scd.2017.0089

    Protein and Molecular Characterization of a Clinically Compliant Amniotic Fluid Stem Cell-Derived Extracellular Vesicle Fraction Capable of Accelerating Muscle Regeneration Through Enhancement of Angiogenesis. / Mellows, Ben; Mitchell, Robert; Antonioli, Manuela; Kretz, Oliver; Chambers, David; Zeuner, Marie Theres; Denecke, Bernd; Musante, Luca; Ramachandra, Durrgah L.; Debacq-Chainiaux, Florence; Holthofer, Harry; Joch, Barbara; Ray, Steve; Widera, Darius; David, Anna L.; Huber, Tobias B.; Dengjel, Joern; De Coppi, Paolo; Patel, Ketan.

    Dans: Stem Cells and Development, Vol 26, Numéro 18, 15.09.2017, p. 1316-1333.

    Résultats de recherche: Contribution à un journal/une revueArticle

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    AU - Mitchell,Robert

    AU - Antonioli,Manuela

    AU - Kretz,Oliver

    AU - Chambers,David

    AU - Zeuner,Marie Theres

    AU - Denecke,Bernd

    AU - Musante,Luca

    AU - Ramachandra,Durrgah L.

    AU - Debacq-Chainiaux,Florence

    AU - Holthofer,Harry

    AU - Joch,Barbara

    AU - Ray,Steve

    AU - Widera,Darius

    AU - David,Anna L.

    AU - Huber,Tobias B.

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