Exosomes: Novel effectors of human platelet lysate activity

E. Torreggiani, F. Perut, L. Roncuzzi, N. Zini, S. R. Baglìo, N. Baldini

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Despite the popularity of platelet-rich plasma (PRP) and platelet lysate (PL) in orthopaedic practice, the mechanism of action and the effectiveness of these therapeutic tools are still controversial. So far, the activity of PRP and PL has been associated with different growth factors (GF) released during platelet degranulation. This study, for the first time, identifies exosomes, nanosized vesicles released in the extracellular compartment by a number of elements, including platelets, as one of the effectors of PL activity. Exosomes were isolated from human PL by differential ultracentrifugation, and analysed by electron microscopy and Western blotting. Bone marrow stromal cells (MSC) treated with three different exosome concentrations (0.6 μg, 5 μg and 50 μg) showed a significant, dose-dependent increase in cell proliferation and migration compared to the control. In addition, osteogenic differentiation assays demonstrated that exosome concentration differently affected the ability of MSC to deposit mineralised matrix. Finally, the analysis of exosome protein content revealed a higher amount of basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF), plateletderived growth factor (PDGF-BB) and transforming growth factor beta 1 (TGF-β1) as compared to PL. In regards to RNA content, an enrichment of small RNAs in exosomes as compared to donor platelets has been found. These results suggest that exosomes consistently contribute to PL activity and could represent an advantageous nanodelivery system for cell-free regeneration therapies.

Original languageEnglish
Pages (from-to)137-151
Number of pages15
JournalEuropean Cells and Materials
Volume28
Publication statusPublished - 2014

Cite this

Torreggiani, E., Perut, F., Roncuzzi, L., Zini, N., Baglìo, S. R., & Baldini, N. (2014). Exosomes: Novel effectors of human platelet lysate activity. European Cells and Materials, 28, 137-151.
Torreggiani, E. ; Perut, F. ; Roncuzzi, L. ; Zini, N. ; Baglìo, S. R. ; Baldini, N. / Exosomes : Novel effectors of human platelet lysate activity. In: European Cells and Materials. 2014 ; Vol. 28. pp. 137-151.
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Torreggiani, E, Perut, F, Roncuzzi, L, Zini, N, Baglìo, SR & Baldini, N 2014, 'Exosomes: Novel effectors of human platelet lysate activity' European Cells and Materials, vol. 28, pp. 137-151.

Exosomes : Novel effectors of human platelet lysate activity. / Torreggiani, E.; Perut, F.; Roncuzzi, L.; Zini, N.; Baglìo, S. R.; Baldini, N.

In: European Cells and Materials, Vol. 28, 2014, p. 137-151.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Exosomes

T2 - Novel effectors of human platelet lysate activity

AU - Torreggiani, E.

AU - Perut, F.

AU - Roncuzzi, L.

AU - Zini, N.

AU - Baglìo, S. R.

AU - Baldini, N.

PY - 2014

Y1 - 2014

N2 - Despite the popularity of platelet-rich plasma (PRP) and platelet lysate (PL) in orthopaedic practice, the mechanism of action and the effectiveness of these therapeutic tools are still controversial. So far, the activity of PRP and PL has been associated with different growth factors (GF) released during platelet degranulation. This study, for the first time, identifies exosomes, nanosized vesicles released in the extracellular compartment by a number of elements, including platelets, as one of the effectors of PL activity. Exosomes were isolated from human PL by differential ultracentrifugation, and analysed by electron microscopy and Western blotting. Bone marrow stromal cells (MSC) treated with three different exosome concentrations (0.6 μg, 5 μg and 50 μg) showed a significant, dose-dependent increase in cell proliferation and migration compared to the control. In addition, osteogenic differentiation assays demonstrated that exosome concentration differently affected the ability of MSC to deposit mineralised matrix. Finally, the analysis of exosome protein content revealed a higher amount of basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF), plateletderived growth factor (PDGF-BB) and transforming growth factor beta 1 (TGF-β1) as compared to PL. In regards to RNA content, an enrichment of small RNAs in exosomes as compared to donor platelets has been found. These results suggest that exosomes consistently contribute to PL activity and could represent an advantageous nanodelivery system for cell-free regeneration therapies.

AB - Despite the popularity of platelet-rich plasma (PRP) and platelet lysate (PL) in orthopaedic practice, the mechanism of action and the effectiveness of these therapeutic tools are still controversial. So far, the activity of PRP and PL has been associated with different growth factors (GF) released during platelet degranulation. This study, for the first time, identifies exosomes, nanosized vesicles released in the extracellular compartment by a number of elements, including platelets, as one of the effectors of PL activity. Exosomes were isolated from human PL by differential ultracentrifugation, and analysed by electron microscopy and Western blotting. Bone marrow stromal cells (MSC) treated with three different exosome concentrations (0.6 μg, 5 μg and 50 μg) showed a significant, dose-dependent increase in cell proliferation and migration compared to the control. In addition, osteogenic differentiation assays demonstrated that exosome concentration differently affected the ability of MSC to deposit mineralised matrix. Finally, the analysis of exosome protein content revealed a higher amount of basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF), plateletderived growth factor (PDGF-BB) and transforming growth factor beta 1 (TGF-β1) as compared to PL. In regards to RNA content, an enrichment of small RNAs in exosomes as compared to donor platelets has been found. These results suggest that exosomes consistently contribute to PL activity and could represent an advantageous nanodelivery system for cell-free regeneration therapies.

KW - Bone marrow stromal cells

KW - Cell-free regeneration therapies

KW - Exosomes

KW - Growth factors

KW - Nanodelivery system

KW - Platelet lysate

KW - Platelet richplasma

KW - RNA

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M3 - Article

VL - 28

SP - 137

EP - 151

JO - European cells & materials

JF - European cells & materials

SN - 1473-2262

ER -

Torreggiani E, Perut F, Roncuzzi L, Zini N, Baglìo SR, Baldini N. Exosomes: Novel effectors of human platelet lysate activity. European Cells and Materials. 2014;28:137-151.