Controlling the fate of regenerative cells with engineered platelet-derived extracellular vesicles

Autor: Ana L. Graça, Manuel Gómez-Florit, Hugo Osório, Márcia T. Rodrigues, Rui M. A. Domingues, Rui L. Reis, Manuela E. Gomes
Přispěvatelé: Universidade do Minho
Rok vydání: 2022
Předmět:
Zdroj: Nanoscale
ISSN: 2040-3372
DOI: 10.1039/d1nr08108j
Popis: Extracellular vesicles (EVs) have emerged as cell-free nanotherapeutic agents for the potential treatment of multiple diseases and for tissue engineering and regenerative medicine strategies. Nevertheless, the field has typically relied on EVs derived from stem cells, the production of which in high quantities and high reproducibility is still under debate. Platelet-derived EVs were produced by a freeze–thaw method of platelet concentrates, a highly available clinical waste material. The aim of this study was to produce and thoroughly characterize platelet-derived EVs and understand their effects in adipose-tissue derived stem cells (hASCs), endothelial cells (HUVECs) and macrophages. Two different EV populations were obtained after differential centrifugation, namely small EVs (sEVs) and medium EVs (mEVs), which showed different size distributions and unique proteomic signatures. EV interaction with hASCs resulted in the modulation of the gene expression of markers related to their commitment toward different lineages. Moreover, mEVs showed higher angiogenic potential than sEVs, in a tube formation assay with HUVECs. Also, the EVs were able to modulate macrophage polarization. Altogether, these results suggest that platelet-derived EVs are promising candidates to be used as biochemical signals or therapeutic tools in tissue engineering and regenerative medicine approaches.
The authors acknowledge ERC CoG MagTendon grant agreement 772817; EC Twinning project Achilles 810850; Fundação para a Ciência e a Tecnologia (FCT) for PhD grant PD/59/2013 and PD/BD/135255/2017, Post-Doc grant SFRH/BPD/112459/2015, CEECIND/01375/2017. Project NORTE-01-0145-FEDER-000021 supported by NORTE2020, under the PORTUGAL2020 Partnership, through the European Regional Development Found and the Portuguese Mass Spectrometry Network, integrated in the National Roadmap of Research Infrastructures of Strategic Relevance (ROTEIRO/0028/2013; LISBOA-01-0145-FEDER-022125). The authors also thank to the Plastic Surgery Department of Hospital da Prelada (Porto, Portugal) and Serviço de Imunohemoterapia do Centro Hospitalar de São João (CHUSJ; Porto, Portugal) for providing adipose tissue samples and platelet concentrates, respectively. Centro de Engenharia Biológica (CEB) of the University of Minho is acknowledged for allowing the use of the ultracentrifuge. Some figures were created with BioRender.com.
Databáze: OpenAIRE