Platelet-Derived Extracellular Vesicles for Regenerative Medicine

Antich-Rosselló, Miquel; Forteza-Genestra, Maria Antònia; Monjo, Marta; Ramis, Joana Maria

doi:10.3390/ijms22168580

Cited by 46 publications

(37 citation statements)

References 69 publications

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“…On the other hand, due to the important role of platelets in the process of thrombosis, these are particularly susceptible to activation during blood collection and handling. This can lead to abundant ex-vivo platelet vesiculation, especially if there is a delay between sample collection and processing ( Brahmer et al, 2019 ; Taus et al, 2019 ; Tripisciano et al, 2020 ; Antich-Rosselló et al, 2021 ; Puhm et al, 2021 ). This uncontrolled release of nonphysiological EVs can adversely affect downstream EV analysis; e.g., it has been shown that contaminating platelet-derived EVs can skew the isolated miRNAs populations in patient and control samples ( Palviainen et al, 2020 ).…”

Section: Contaminants Of Extracellular Vesicle Isolates From Blood Plasma and Their Relevance For Extracellular Vesicle Isolation And Chamentioning

confidence: 99%

Blood Nanoparticles – Influence on Extracellular Vesicle Isolation and Characterization

2021

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Blood is a rich source of disease biomarkers, which include extracellular vesicles (EVs). EVs are nanometer-to micrometer-sized spherical particles that are enclosed by a phospholipid bilayer and are secreted by most cell types. EVs reflect the physiological cell of origin in terms of their molecular composition and biophysical characteristics, and they accumulate in blood even when released from remote organs or tissues, while protecting their cargo from degradation. The molecular components (e.g., proteins, miRNAs) and biophysical characteristics (e.g., size, concentration) of blood EVs have been studied as biomarkers of cancers and neurodegenerative, autoimmune, and cardiovascular diseases. However, most biomarker studies do not address the problem of contaminants in EV isolates from blood plasma, and how these might affect downstream EV analysis. Indeed, nonphysiological EVs, protein aggregates, lipoproteins and viruses share many molecular and/or biophysical characteristics with EVs, and can therefore co-isolate with EVs from blood plasma. Consequently, isolation and downstream analysis of EVs from blood plasma remain a unique challenge, with important impacts on the outcomes of biomarker studies. To help improve rigor, reproducibility, and reliability of EV biomarker studies, we describe here the major contaminants of EV isolates from blood plasma, and we report on how different EV isolation methods affect their levels, and how contaminants that remain can affect the interpretation of downstream EV analysis.

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Section: Contaminants Of Extracellular Vesicle Isolates From Blood Plasma and Their Relevance For Extracellular Vesicle Isolation And Chamentioning

confidence: 99%

Blood Nanoparticles – Influence on Extracellular Vesicle Isolation and Characterization

2021

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“…In this context, platelet EVs are a potential and underexplored source of sorted bioactive molecules, including different growth factors [ 23 ], that can overcome some of the aforementioned limitations. Platelet EVs offer unprecedented perspectives for personalized therapies, since they can be obtained from autologous sources from a simple blood extraction [ 8 , 22 , 24 , 25 ]. Moreover, platelet EVs can also be obtained on a large scale from otherwise discarded expired platelet units for clinical use, and have low batch-to-batch variability in terms of growth factors composition [ 18 , 26 ], which would be reflected in EVs with a more standardized biomolecule signature.…”

Section: Introductionmentioning

confidence: 99%

Therapeutic Effects of Platelet-Derived Extracellular Vesicles in a Bioengineered Tendon Disease Model

Graça

Domingues

Calejo

et al. 2022

IJMS

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Tendon injuries represent over 30–50% of musculoskeletal disorders worldwide, yet the available therapies do not provide complete tendon repair/regeneration and full functionality restoring. Extracellular vesicles (EVs), membrane-enclosed nanoparticles, have emerged as the next breakthrough in tissue engineering and regenerative medicine to promote endogenous tissue regeneration. Here, we developed a 3D human in vitro model mimicking the signature of pathological tendon and used it to evaluate the influence that different platelet-derived EVs might have in tendon tissue repair mechanisms. For this, different EV populations isolated from platelets, small EVs (sEVs) and medium EVs (mEVs), were added to the culture media of human tendon-derived cells (hTDCs) cultured on isotropic nanofibrous scaffolds. The platelet-derived EVs increased the expression of tenogenic markers, promoted a healthy extracellular matrix (ECM) remodeling, and the synthesis of anti-inflammatory mediators. These findings suggest that platelet EVs provided relevant biochemical cues that potentiated a recovery of hTDCs phenotype from a diseased to a healthy state. Thus, this study opens new perspectives for the translation of platelet-derived EVs as therapeutics.

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“…1e). According to the Minimal Information for Studies of Extracellular Vesicles (“MISEV”) guidelines 58 , TEM was qualitatively implemented by both Western Blot showing the positive expression of the proteins ALIX, CD9, Annexin A1, TSG101 (cytosolic, membrane and marker of biogenesis of EV) in PL-derived EVs 60,61 and negative expression for calnexin, therefore suggesting the absence of nonEV structures in the preparation of EVs 62 (Fig. 1f).…”

Section: Resultsmentioning

confidence: 99%

“Human platelet lysate derived extracellular vesicles enhance angiogenesis through miR-126”

Bordin

Chirivì

Pagano

et al. 2022

Preprint

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Objectivesextracellular vesicles (EVs) represent key biological mediators of several physiological functions within the cell microenvironment. Platelets are the most abundant source of EVs in the blood, contributing to the plastic and versatile behaviour of these cells. Similarly, platelet lysate (PL), the best angiogenic performer of platelet origin and routinely employed 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 contained in PL, by investigating the biological and molecular features related to the angiogenic capacity extrapolated from that possessed by PL.Methodswe tested angiogenic ability and molecular cargo in 3D bioprinted models and by RNA sequencing analysis of PL-derived EVs.Resultsa subset of small vesicles is highly represented in PL. The EVs did not retain aggregation ability, but they preserved a low redox state in endothelial cells and significantly increased the formation of angiogenic tubularly-like structures in 3D endothelial bioprinted constructs. EVs resembled the miRNome profile of PL, mainly enriched of small RNAs and of a high amount of miR-126, the most abundant angiogenic miRNA of platelet origin. The transfer of miR-126 in endothelial cells by EVs after the in vitro inhibition of the endogenous miR-126, restored the angiogenic effects of PL-derived EVs.ConclusionsPL 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.

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Platelet-Derived Extracellular Vesicles for Regenerative Medicine

Cited by 46 publications

References 69 publications

Blood Nanoparticles – Influence on Extracellular Vesicle Isolation and Characterization

Blood Nanoparticles – Influence on Extracellular Vesicle Isolation and Characterization

Therapeutic Effects of Platelet-Derived Extracellular Vesicles in a Bioengineered Tendon Disease Model

“Human platelet lysate derived extracellular vesicles enhance angiogenesis through miR-126”

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