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Platelets’ Role in Dentistry: From Oral Pathology to Regenerative Potential
 
 
Article

Synergy of Human Platelet-Derived Extracellular Vesicles with Secretome Proteins Promotes Regenerative Functions

1
Cell Therapy Institute, Spinal Cord Injury and Tissue Regeneration Center Salzburg (SCI-TReCS), Paracelsus Medical University (PMU), 5020 Salzburg, Austria
2
Department of Transfusion Medicine and SCI-TReCS, Paracelsus Medical University (PMU), 5020 Salzburg, Austria
3
Department for Biosciences and Medical Biology, Paris Lodron University, 5020 Salzburg, Austria
*
Author to whom correspondence should be addressed.
Academic Editor: Catherine Strassel
Biomedicines 2022, 10(2), 238; https://doi.org/10.3390/biomedicines10020238
Received: 22 December 2021 / Revised: 17 January 2022 / Accepted: 19 January 2022 / Published: 23 January 2022
(This article belongs to the Special Issue Biogenesis and Functions of Blood Platelets)
Platelet-rich plasma is a promising regenerative therapeutic with controversial efficacy. We and others have previously demonstrated regenerative functions of human platelet lysate (HPL) as an alternative platelet-derived product. Here we separated extracellular vesicles (EVs) from soluble factors of HPL to understand the mode of action during skin-organoid formation and immune modulation as model systems for tissue regeneration. HPL-EVs were isolated by tangential-flow filtration (TFF) and further purified by size-exclusion chromatography (SEC) separating EVs from (lipo)protein-enriched soluble fractions. We characterized samples by tunable resistive pulse sensing, western blot, tandem mass-tag proteomics and super-resolution microscopy. We evaluated EV function during angiogenesis, wound healing, organoid formation and immune modulation. We characterized EV enrichment by TFF and SEC according to MISEV2018 guidelines. Proteomics showed three major clusters of protein composition separating TSEC-EVs from HPL clustering with TFF soluble fractions and TFF-EVs clustering with TSEC soluble fractions, respectively. HPL-derived TFF-EVs promoted skin-organoid formation and inhibited T-cell proliferation more efficiently than TSEC-EVs or TSEC-soluble fractions. Recombining TSEC-EVs with TSEC soluble fractions re-capitulated TFF-EV effects. Zeta potential and super-resolution imaging further evidenced protein corona formation on TFF-EVs. Corona depletion on SEC-EVs could be artificially reconstituted by TSEC late fraction add-back. In contrast to synthetic nanoparticles, which commonly experience reduced function after corona formation, the corona-bearing EVs displayed improved functionality. We conclude that permissive isolation technology, such as TFF, and better understanding of the mechanism of EV corona function are required to realize the complete potential of platelet-based regenerative therapies. View Full-Text
Keywords: human platelet lysate (HPL); platelet-rich plasma (PRP); extracellular vesicles (EVs); corona; skin regeneration; immune modulation; angiogenesis human platelet lysate (HPL); platelet-rich plasma (PRP); extracellular vesicles (EVs); corona; skin regeneration; immune modulation; angiogenesis
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MDPI and ACS Style

Gomes, F.G.; Andrade, A.C.; Wolf, M.; Hochmann, S.; Krisch, L.; Maeding, N.; Regl, C.; Poupardin, R.; Ebner-Peking, P.; Huber, C.G.; Meisner-Kober, N.; Schallmoser, K.; Strunk, D. Synergy of Human Platelet-Derived Extracellular Vesicles with Secretome Proteins Promotes Regenerative Functions. Biomedicines 2022, 10, 238. https://doi.org/10.3390/biomedicines10020238

AMA Style

Gomes FG, Andrade AC, Wolf M, Hochmann S, Krisch L, Maeding N, Regl C, Poupardin R, Ebner-Peking P, Huber CG, Meisner-Kober N, Schallmoser K, Strunk D. Synergy of Human Platelet-Derived Extracellular Vesicles with Secretome Proteins Promotes Regenerative Functions. Biomedicines. 2022; 10(2):238. https://doi.org/10.3390/biomedicines10020238

Chicago/Turabian Style

Gomes, Fausto Gueths, André Cronemberger Andrade, Martin Wolf, Sarah Hochmann, Linda Krisch, Nicole Maeding, Christof Regl, Rodolphe Poupardin, Patricia Ebner-Peking, Christian G. Huber, Nicole Meisner-Kober, Katharina Schallmoser, and Dirk Strunk. 2022. "Synergy of Human Platelet-Derived Extracellular Vesicles with Secretome Proteins Promotes Regenerative Functions" Biomedicines 10, no. 2: 238. https://doi.org/10.3390/biomedicines10020238

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