Differential Therapeutic Effect of Extracellular Vesicles Derived by Bone Marrow and Adipose Mesenchymal Stem Cells on Wound Healing of Diabetic Ulcers and Correlation to Their Cargoes

Extracellular vesicles (EVs) derived from mesenchymal stem cells isolated from both bone marrow (BMSCs) and adipose tissue (ADSCs) show potential therapeutic effects. These vesicles often show a similar beneficial effect on tissue regeneration, but in some contexts, they exert different biological p...

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Main Authors: Margherita Pomatto, Chiara Gai, Federica Negro, Massimo Cedrino, Cristina Grange, Elena Ceccotti, Gabriele Togliatto, Federica Collino, Marta Tapparo, Federico Figliolini, Tatiana Lopatina, Maria Felice Brizzi, Giovanni Camussi
Format: Article
Language:English
Published: MDPI AG 2021-04-01
Series:International Journal of Molecular Sciences
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Online Access:https://www.mdpi.com/1422-0067/22/8/3851
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author Margherita Pomatto
Chiara Gai
Federica Negro
Massimo Cedrino
Cristina Grange
Elena Ceccotti
Gabriele Togliatto
Federica Collino
Marta Tapparo
Federico Figliolini
Tatiana Lopatina
Maria Felice Brizzi
Giovanni Camussi
author_facet Margherita Pomatto
Chiara Gai
Federica Negro
Massimo Cedrino
Cristina Grange
Elena Ceccotti
Gabriele Togliatto
Federica Collino
Marta Tapparo
Federico Figliolini
Tatiana Lopatina
Maria Felice Brizzi
Giovanni Camussi
author_sort Margherita Pomatto
collection DOAJ
description Extracellular vesicles (EVs) derived from mesenchymal stem cells isolated from both bone marrow (BMSCs) and adipose tissue (ADSCs) show potential therapeutic effects. These vesicles often show a similar beneficial effect on tissue regeneration, but in some contexts, they exert different biological properties. To date, a comparison of their molecular cargo that could explain the different biological effect is not available. Here, we demonstrated that ADSC-EVs, and not BMSC-EVs, promote wound healing on a murine model of diabetic wounds. Besides a general similarity, the bioinformatic analysis of their protein and miRNA cargo highlighted important differences between these two types of EVs. Molecules present exclusively in ADSC-EVs were highly correlated to angiogenesis, whereas those expressed in BMSC-EVs were preferentially involved in cellular proliferation. Finally, in vitro analysis confirmed that both ADSC and BMSC-EVs exploited beneficial effect on cells involved in skin wound healing such as fibroblasts, keratinocytes and endothelial cells, but through different cellular processes. Consistent with the bioinformatic analyses, BMSC-EVs were shown to mainly promote proliferation, whereas ADSC-EVs demonstrated a major effect on angiogenesis. Taken together, these results provide deeper comparative information on the cargo of ADSC-EVs and BMSC-EVs and the impact on regenerative processes essential for diabetic wound healing.
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spelling doaj.art-2dade8e51caf42a7ab3fe39be0016a582023-11-21T14:38:48ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-04-01228385110.3390/ijms22083851Differential Therapeutic Effect of Extracellular Vesicles Derived by Bone Marrow and Adipose Mesenchymal Stem Cells on Wound Healing of Diabetic Ulcers and Correlation to Their CargoesMargherita Pomatto0Chiara Gai1Federica Negro2Massimo Cedrino3Cristina Grange4Elena Ceccotti5Gabriele Togliatto6Federica Collino7Marta Tapparo8Federico Figliolini9Tatiana Lopatina10Maria Felice Brizzi11Giovanni Camussi12Department of Medical Sciences, University of Turin, 10126 Turin, ItalyDepartment of Medical Sciences, University of Turin, 10126 Turin, ItalyUnicyte Srl, 10126 Turin, Italy2i3T Scarl University of Turin, 10126 Turin, ItalyDepartment of Medical Sciences, University of Turin, 10126 Turin, ItalyDepartment of Medical Sciences, University of Turin, 10126 Turin, ItalyDepartment of Medical Sciences, University of Turin, 10126 Turin, ItalyLaboratory of Translational Research in Paediatric Nephro-urology, Fondazione Ca’ Granada IRCCS Ospedale Maggiore Policlinico, 20122 Milan, ItalyDepartment of Medical Sciences, University of Turin, 10126 Turin, Italy2i3T Scarl University of Turin, 10126 Turin, ItalyDepartment of Medical Sciences, University of Turin, 10126 Turin, ItalyDepartment of Medical Sciences, University of Turin, 10126 Turin, ItalyDepartment of Medical Sciences, University of Turin, 10126 Turin, ItalyExtracellular vesicles (EVs) derived from mesenchymal stem cells isolated from both bone marrow (BMSCs) and adipose tissue (ADSCs) show potential therapeutic effects. These vesicles often show a similar beneficial effect on tissue regeneration, but in some contexts, they exert different biological properties. To date, a comparison of their molecular cargo that could explain the different biological effect is not available. Here, we demonstrated that ADSC-EVs, and not BMSC-EVs, promote wound healing on a murine model of diabetic wounds. Besides a general similarity, the bioinformatic analysis of their protein and miRNA cargo highlighted important differences between these two types of EVs. Molecules present exclusively in ADSC-EVs were highly correlated to angiogenesis, whereas those expressed in BMSC-EVs were preferentially involved in cellular proliferation. Finally, in vitro analysis confirmed that both ADSC and BMSC-EVs exploited beneficial effect on cells involved in skin wound healing such as fibroblasts, keratinocytes and endothelial cells, but through different cellular processes. Consistent with the bioinformatic analyses, BMSC-EVs were shown to mainly promote proliferation, whereas ADSC-EVs demonstrated a major effect on angiogenesis. Taken together, these results provide deeper comparative information on the cargo of ADSC-EVs and BMSC-EVs and the impact on regenerative processes essential for diabetic wound healing.https://www.mdpi.com/1422-0067/22/8/3851wound healingMSCexosomeextracellular vesiclediabetesadipose
spellingShingle Margherita Pomatto
Chiara Gai
Federica Negro
Massimo Cedrino
Cristina Grange
Elena Ceccotti
Gabriele Togliatto
Federica Collino
Marta Tapparo
Federico Figliolini
Tatiana Lopatina
Maria Felice Brizzi
Giovanni Camussi
Differential Therapeutic Effect of Extracellular Vesicles Derived by Bone Marrow and Adipose Mesenchymal Stem Cells on Wound Healing of Diabetic Ulcers and Correlation to Their Cargoes
International Journal of Molecular Sciences
wound healing
MSC
exosome
extracellular vesicle
diabetes
adipose
title Differential Therapeutic Effect of Extracellular Vesicles Derived by Bone Marrow and Adipose Mesenchymal Stem Cells on Wound Healing of Diabetic Ulcers and Correlation to Their Cargoes
title_full Differential Therapeutic Effect of Extracellular Vesicles Derived by Bone Marrow and Adipose Mesenchymal Stem Cells on Wound Healing of Diabetic Ulcers and Correlation to Their Cargoes
title_fullStr Differential Therapeutic Effect of Extracellular Vesicles Derived by Bone Marrow and Adipose Mesenchymal Stem Cells on Wound Healing of Diabetic Ulcers and Correlation to Their Cargoes
title_full_unstemmed Differential Therapeutic Effect of Extracellular Vesicles Derived by Bone Marrow and Adipose Mesenchymal Stem Cells on Wound Healing of Diabetic Ulcers and Correlation to Their Cargoes
title_short Differential Therapeutic Effect of Extracellular Vesicles Derived by Bone Marrow and Adipose Mesenchymal Stem Cells on Wound Healing of Diabetic Ulcers and Correlation to Their Cargoes
title_sort differential therapeutic effect of extracellular vesicles derived by bone marrow and adipose mesenchymal stem cells on wound healing of diabetic ulcers and correlation to their cargoes
topic wound healing
MSC
exosome
extracellular vesicle
diabetes
adipose
url https://www.mdpi.com/1422-0067/22/8/3851
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