Human platelet lysate-derived extracellular vesicles enhanceangiogenesis through miR-126
Creators
- Antonella Bordin1
- Maila Chirivì2
- Francesca Pagano3
- Marika Milan4
- Marco Iuliano1
- Eleonora Scaccia5
- Orazio Fortunato6
- Giorgio Mangino1
- Xhulio Dhori1
- Elisabetta De Marinis1
- Alessandra D'Amico7
- Selenia Miglietta8
- Vittorio Picchio1
- Roberto Rizzi9
- Giovanna Romeo1
- Fabio Pulcinelli10
- Isotta Chimenti1
- Giacomo Frati1
- Elena De Falco1
- 1. Department of Medical-Surgical Sciences and Biotechnologies, Sapienza University of Rome,
- 2. Department of Pathophysiology and Transplantation, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Milan
- 3. Institute of Biochemistry and Cell Biology, National Research Council of Italy (IBBC-CNR), Monterotondo
- 4. UOC Neurologia, Fondazione Ca'Granda, Ospedale Maggiore Policlinico, Milan
- 5. Institute of Transfusion Medicine and Immunology, Mannheim Institute of Innate Immunoscience, Medical Faculty Mannheim, Heidelberg University
- 6. Tumor Genomics Unit, Department of Research, IRCCS Fondazione Istituto Nazionale dei Tumori, Milan
- 7. Department of Movement, Human and Health Sciences, University of Rome"Foro Italico"
- 8. Department of Anatomy, Histology, Forensic Medicine and Orthopaedics, La Sapienza University of Rome
- 9. Istituto Nazionale Genetica Molecolare INGM'Romeo ed Enrica Invernizzi',
- 10. Department of Translational and Precision Medicine, Sapienza University of Rome
Description
Objectives
Extracellular vesicles (EVs) are key biological mediators of several physiological functions within the cell microenvironment. Platelets are the most abundant source of EVs in the blood. Similarly, platelet lysate (PL), the best platelet derivative and angiogenic performer for regenerative purposes, is enriched of EVs, but their role is still too poorly discovered to be suitably exploited. Here, we explored the contribution of the EVs in PL, by investigating the angiogenic features extrapolated from that possessed by PL.
Methods
We tested angiogenic ability and molecular cargo in 3D bioprinted models and by RNA sequencing analysis of PL-derived EVs.
Results
A subset of small vesicles is highly represented in PL. The EVs do not retain aggregation ability, preserving a low redox state in human umbilical vein endothelial cells (HUVECs) and increasing the angiogenic tubularly-like structures in 3D endothelial bioprinted constructs. EVs resembled the miRNome profile of PL, mainly enriched with small RNAs and a high amount of miR-126, the most abundant angiogenic miRNA in platelets. The transfer of miR-126 by EVs in HUVEC after the in vitro inhibition of the endogenous form, restored angiogenesis, without involving VEGF as a downstream target in this system.
Conclusion
PL is a biological source of available EVs with angiogenic effects involving a miRNAs-based cargo. These properties can be exploited for targeted molecular/biological manipulation of PL, by potentially developing a product exclusively manufactured of EVs.
Notes
Files
Cell Proliferation - 2022 - Bordin - Human platelet lysate‐derived extracellular vesicles enhance angiogenesis through.pdf
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