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Advances in bioengineering pancreatic tumor-stroma physiomimetic Biomodels
Monteiro, Maria V.; Ferreira, Luís P.; Rocha, Marta; Gaspar, Vítor M.; Mano, João F.Pancreatic cancer exhibits a unique bioarchitecture and desmoplastic cancer-stoma interplay that governs disease progression, multi-resistance, and metastasis. Emulating the biological features and microenvironment heterogeneity of pancreatic cancer stroma in vitro is remarkably complex, yet highly desirable for advancing the discovery of innovative therapeutics. Diverse bioengineering approaches exploiting pat...
Advancing tissue decellularized hydrogels for engineering human organoids
Moura, Beatriz S.; Monteiro, Maria V.; Ferreira, Luís P.; Lavrador, Pedro; Gaspar, Vítor M.; Mano, João F.The extracellular matrix plays a critical role in bioinstructing cellular self-assembly and spatial (re)configuration processes that culminate in human organoids in vitro generation and maturation. Considering the importance of the supporting matrix, herein we showcase the most recent advances in the bioengineering of decellularized tissue hydrogels for generating organoids and assembloids. Key design blueprint...
Organotypic 3D decellularized matrix tumor spheroids for high-throughput drug s...
Ferreira, Luís P.; Gaspar, Vítor M.; Mendes, Luís; Duarte, Iola F.; Mano, João F.Decellularized extracellular matrix (dECM) is emerging as a valuable tool for generating 3D in vitro tumor models that better recapitulate tumor-stroma interactions. However, the development of dECM-3D heterotypic microtumors exhibiting a controlled morphology is yet to be materialized. Precisely controlling microtumors morphologic features is key to avoid an inaccurate evaluation of therapeutics performance du...
Screening of dual chemo-photothermal cellular nanotherapies in organotypic brea...
Ferreira, Luís P.; Gaspar, Vítor M.; Monteiro, Maria V.; Freitas, Bruno; Silva, Nuno J. O.; Mano, João F.Living therapeutics approaches that exploit mesenchymal stem cells (MSCs) as nanomedicine carriers are highly attractive due to MSCs native tropism toward the 3D tumor microenvironment. However, a streamlined pre-clinical evaluation of nano-in-cell anti-cancer therapies remains limited by the lack of in vitro testing platforms for screening MSCs-3D microtumor interactions. Herein we generated dense breast cance...
Bioimaging of mesenchymal stem cells spatial distribution and interactions with...
Ferreira, Luís P.; Gaspar, Vítor M.; Mano, João F.In solid tumors, mesenchymal stem cells (MSCs) are recognized to establish complex intercommunication networks with cancer cells and to significantly influence their invasion and metastasis potential. Such bidirectional interplay occurs between both tissue resident/tumor-associated MSCs (TA-MSCs) and also tumor infiltrating MSCs (TM-MSCs) that migrate from distant sites such as the bone marrow. Interestingly, m...
Hydrogel 3D in vitro tumor models for screening cell aggregation mediated drug ...
Monteiro, Maria V.; Gaspar, Vítor M.; Ferreira, Luís P.; Mano, João F.Hydrogel-based 3D in vitro models comprising tumor ECM-mimetic biomaterials exhibit superlative potential as preclinical testing platforms for drug discovery and bioperformance screening. However, during hydrogel design and testing stages, the ideal selection between cancer cell laden 3D models or spheroid embedded hydrogel platforms remains to be elucidated. Selecting a disease-mimicking cellular arrangement w...
Decellularized extracellular matrix for bioengineering physiomimetic 3D in Vitr...
Ferreira, Luís P.; Gaspar, Vítor M.; Mano, João F.Recent advances in the extraction and purification of decellularized extracellular matrix (dECM) obtained from healthy or malignant tissues open new avenues for engineering physiomimetic 3D in vitro tumor models, which closely recapitulate key biomolecular hallmarks and the dynamic cancer cell-ECM interactions in the tumor microenvironment. We review current and upcoming methodologies for chemical modification ...
Mesenchymal stem cells relevance in multicellular bioengineered 3D In vitro tum...
Ferreira, Luís P.; Gaspar, Vítor M.; Henrique, Rui; Jerónimo, Carmen; Mano, João F.In vitro 3D tumor microenvironment mimicking models are gathering momentum as alternatives to traditional 2D flat monolayer cultures due to their potential for recapitulating major cancer hallmarks. To fulfill such potential, it is crucial that 3D tumor testing platforms completely emulate in vitro the complex in vivo tumor niche and its cellular constituents. Mesenchymal stem cells (MSCs) are recognized to pla...