by Keyword: Cell-derived matrices

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Rubi-Sans, G., Castaño, O., Cano, I., Mateos-Timoneda, M. A., Perez-Amodio, S., Engel, E., (2020). Engineering cell-derived matrices: From 3D models to advanced personalized therapies Advanced Functional Materials 30, (44), e2000496

Regenerative medicine and disease models have evolved in recent years from two to three dimensions, providing in vitro constructs that are more similar to in vivo tissues. By mimicking native tissues, cell-derived matrices (CDMs) have emerged as new modifiable extracellular matrices for a variety of tissues, allowing researchers to study basic cellular processes in tissue-like structures, test tissue regeneration approaches, and model disease development. In this review, different fabrication techniques and characterization methods of CDMs are presented and examples of their application in cell behavior studies, tissue regeneration, and disease models are provided. In addition, future guidelines and perspectives in the field of CDMs are discussed.

Keywords: 3D models, Biomaterials, Cell-derived matrices, Extracellular matrix, Personalized therapies

Almici, Enrico, Caballero, David, Montero, Joan, Samitier, Josep, (2020). 3D neuroblastoma in vitro models using engineered cell-derived matrices Biomaterials for 3D Tumor Modeling (ed. Kundu, Subhas C., Reis, Rui L.), Elsevier (Amsterdam, Netherlands) , 107-130

Neuroblastoma (NB) is a malignant tumor that affects the peripheral nervous system and represents one of the most frequent cancers in infants. Its prognosis is poor in older patients and the presence of genetic abnormalities. Metastasis is often present at the time of diagnosis, making treatment more intensive and unsuccessful. Poor prognosis and variable treatment efficacy require a better understanding of the underlying biology. Evidence has shown that the tumor microenvironment is the characteristic of tumor malignancy and progression. A more highly differentiated tissue phenotype represents a positive prognostic marker, while the tumoral tissue is characterized by a distinct composition and morphology of the extracellular matrix (ECM). In this chapter, we discuss the application of decellularized cell-derived matrices (CDMs) to model in vitro the morphology of the ECM encountered in histological hallmarks of NB patients. This technique allows for the in vitro reproduction of the fine structure and composition of native microenvironments. Because of recent advances in culture systems and decellularization techniques, it is possible to engineer CDM composition and microarchitecture to produce differentiated models of tissue niches. The final goal is to repopulate the “scaffold” with malignant NB cells for drug screening and target discovery applications, studying the impact of patient-inspired tissues on signaling, migration, and tissue remodeling.

Keywords: Neuroblastoma, Cancer, Bioengineering, Tumor microenvironment, Cell-derived matrices, Decellularization

Caballero, D., Samitier, J., (2017). Topological control of extracellular matrix growth: A native-like model for cell morphodynamics studies ACS Applied Materials & Interfaces 9, (4), 4159-4170

The interaction of cells with their natural environment influences a large variety of cellular phenomena, including cell adhesion, proliferation, and migration. The complex extracellular matrix network has challenged the attempts to replicate in vitro the heterogeneity of the cell environment and has threatened, in general, the relevance of in vitro studies. In this work, we describe a new and extremely versatile approach to generate native-like extracellular matrices with controlled morphologies for the in vitro study of cellular processes. This general approach combines the confluent culture of fibroblasts with microfabricated guiding templates to direct the three-dimensional growth of well-defined extracellular networks which recapitulate the structural and biomolecular complexity of features typically found in vivo. To evaluate its performance, we studied fundamental cellular processes, including cell cytoskeleton organization, cell-matrix adhesion, proliferation, and protrusions morphodynamics. In all cases, we found striking differences depending on matrix architecture and, in particular, when compared to standard two-dimensional environments. We also assessed whether the engineered matrix networks influenced cell migration dynamics and locomotion strategy, finding enhanced migration efficiency for cells seeded on aligned matrices. Altogether, our methodology paves the way to the development of high-performance models of the extracellular matrix for potential applications in tissue engineering, diagnosis, or stem-cell biology.

Keywords: Biomimetics, Cell migration, Engineered cell-derived matrices, Extracellular matrix, In vitro model