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Extracellular vesicles enriched with an endothelial cell pro-survival microRNA ...

Fernandes, Hugo; Zonnari, Alessandra; Abreu, Ricardo Cerqueira de; Aday, Sezin; Barão, Marta; Albino, Inês; Lino, Miguel; Branco, Ana; Seabra, Cátia

Endothelial cell (EC) activity is essential for tissue regeneration in several (patho)physiological contexts. However, our capacity to deliver in vivo biomolecules capable of controlling EC fate is relatively limited. Here, we screened a library of microRNA (miR) mimics and identified 25 miRs capable of enhancing the survival of ECs exposed to ischemia-mimicking conditions. In vitro, we showed that miR-425-5p, ...


Antimicrobial peptide-gold nanoscale therapeutic formulation with high skin reg...

Comune, Michela; Rai, Akhilesh; Chereddy, Kiran K; Pinto, Sandra; Aday, Sezin; Ferreira, André F; Zonari, Alessandra; Blersch, Josephine

Chronic skin wounds affect ≈3% of persons aged >60years (Davies et al., 2007) [1]. These wounds are typically difficult to heal by conventional therapies and in many cases they get infected making even harder the regeneration process. The antimicrobial peptide (AMP) LL37 combines antimicrobial with pro-regenerative properties and thus represents a promising topical therapy to address both problems. Here, we inv...


Synthetic microparticles conjugated with VEGF165 improve the survival of endoth...

Aday, Sezin; Zoldan, Janet; Besnier, Marie; Carreto, Laura; Saif, Jaimy; Fernandes, Rui; Santos, Tiago; Bernardino, Liliana Inácio; Langer, Robert

Several cell-based therapies are under pre-clinical and clinical evaluation for the treatment of ischemic diseases. Poor survival and vascular engraftment rates of transplanted cells force them to work mainly via time-limited paracrine actions. Although several approaches, including the use of soluble vascular endothelial growth factor (sVEGF)-VEGF165, have been developed in the last 10 years to enhance cell su...


Lysophosphatidic acid enhances survival of human CD34(+) cells in ischemic cond...

Kostic, Ivana; Fidalgo-Carvalho, Isabel; Aday, Sezin; Vazão, Helena; Carvalheiro, Tiago; Grãos, Mário; Duarte, António; Cardoso, Carla; Gonçalves, Lino

Several clinical trials are exploring therapeutic effect of human CD34(+) cells in ischemic diseases, including myocardial infarction. Unfortunately, most of the cells die few days after delivery. Herein we show that lysophosphatidic acid (LPA)-treated human umbilical cord blood-derived CD34(+) cells cultured under hypoxic and serum-deprived conditions present 2.2-fold and 1.3-fold higher survival relatively to...


A stable and reproducible human blood-brain barrier model derived from hematopo...

Cecchelli, Romeo; Aday, Sezin; Sevin, Emmanuel; Almeida, Catarina; Culot, Maxime; Dehouck, Lucie; Coisne, Caroline; Engelhardt, Britta

The human blood brain barrier (BBB) is a selective barrier formed by human brain endothelial cells (hBECs), which is important to ensure adequate neuronal function and protect the central nervous system (CNS) from disease. The development of human in vitro BBB models is thus of utmost importance for drug discovery programs related to CNS diseases. Here, we describe a method to generate a human BBB model using c...


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