Cancer remains a serious burden in society and while the pace in the development of novel and more effective therapeutics is increasing, testing platforms that faithfully mimic the tumor microenvironment are lacking. With a clear shift from animal models to more complex in vitro 3D systems, spheroids emerge as strong options in this regard. Years of development have allowed spheroid-based models to better repro...
Tese de doutoramento em Engenharia de Tecidos, Medicina Regenerativa e Células Estaminais; Cancer is a global pandemic with a high incidence among the world population and effective treatments are for the most part elusive. The tumor microenvironment is a highly complex and heterotypic mixture of cells that interact to regulate central control mechanisms, driving immunosuppression and promoting both survival an...
In vitro prevascularization is one of the most explored approaches to foster engineered tissue vascularization. We previously demonstrated a benefit in tissue neovascularization by using integrin-specific biomaterials prevascularized by stromal vascular fraction (SVF) cells, which triggered vasculogenesis in the absence of extrinsic growth factors. SVF cells are also associated to biological processes important...
Background: T cell priming has been shown to be a powerful immunotherapeutic approach for cancer treatment in terms of efcacy and relatively weak side efects. Systems that optimize the stimulation of T cells to improve therapeutic efcacy are therefore in constant demand. A way to achieve this is through artifcial antigen presenting cells that are complexes between vehicles and key molecules that target relevant...
Integrin-binding biomaterials have been extensively evaluated for their capacity to enable de novo formation of capillary-like structures/vessels, ultimately supporting neovascularization in vivo. Yet, the role of integrins as vascular initiators in engineered materials is still not well understood. Here, we show that αvβ3 integrin-specific 3D matrices were able to retain PECAM1+ cells from the stromal vascu...
The advances achieved by cell-based therapies to treat autoimmune diseases such as rheumatoid arthritis (RA) and multiple sclerosis (MS), despite promising, are still insufficient for the current demands. RA and MS therapeutic approaches follow world guidelines to use disease modifying drugs and biological agents that, regardless of some good results in clinical outcomes, are well known for several systemic sec...
Fibroblasts are key players in the scarring process. In hypertrophic scars, fibroblasts suffer phenotypical changes into myofibroblasts persisting in the wound under the influence of local biochemical (TGFb1) and biomechanical signaling leading to enhanced immature extracellular matrix (ECM) synthesis. Benchtop models of hypertrophic scars rely on scarce human ex vivo samples or standard 2D cultures of hypertro...
Regardless of the advances in understanding the mechanisms and the pathophysiology behind skin deformities, scaring continues to be an unsolved clinical problem. The underlying wound healing process involves a series of key cells which play different key roles. Fibroblasts are known to suffer the influence of local biochemical (e.g TGF-B1) and biomechanical signaling upon a wound scenario leading to a phenotypi...
The detailed pathophysiology of diabetic foot ulcers is yet to be established and improved treatments are still required. We propose a strategy that directs inflammation, neovascularization, and neoinnervation of diabetic wounds. Aiming to potentiate a relevant secretome for nerve regeneration, stem cells were precultured in hyaluronic acid-based spongy hydrogels under neurogenic/standard media before transplan...
Prostate cancer is one of the most diagnosed diseases in men at the present time. It is well known that changes in calcium (Ca2+) homeostasis are derived from modifications in Ca2+ regulating elements. Regucalcin (RGN) is a Ca2+-binding protein which plays an important role in maintenance of intracellular Ca2+ homeostasis and regulation of apoptosis and proliferation. RGN is underexpressed in prostate cancer ce...