[SCAN] Exploiting 3D cell culture to model cellular microenvironment in disease

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Title: Exploiting 3D cell culture to model cellular microenvironment in disease

Speaker: Catarina Brito

Affiliation: Advanced Cell Models Lab, ITQB NOVA

Abstract:

The cellular microenvironment influences cell behavior and modulates many physiological functions and pathological processes. There is increasing awareness that the different cellular players of a specific tissue as well as the heterogeneous molecular components that constitute the extracellular space (e.g., ECM, soluble factors, microvesicles) influence disease progression and therapeutic response. The major challenge in studying the underlying mechanisms is the lack of human cell models in which the different contributing cell types are represented and the dynamics of the cellular and extracellular spaces recapitulated without the confounding effects of heterologous ECM and soluble factors. To overcome these challenges we develop disease cell models, applying advanced cell culture approaches (3D culture, co-culture, cell immobilization) and systems (perfusion, bioreactors) to human stem cells and other patient-derived cells.

I will discuss recent data on two of the main research lines in the lab. One is focused on the development of 3D cell models for recapitulation of human brain microenvironment. We have shown that differentiation of human induced pluripotent stem cells (hiPSC) as neurospheroids, in perfusion stirred tank bioreactors, promotes the expression of cellular and extracellular features found in neural tissue. We are now applying the neurospheroid model to address molecular defects in cell-ECM interactions associated with Mucopolysaccharidosis type VII (MPS VII), a lysosomal storage disease caused by deficient β-glucuronidase (β-gluc) activity, which leads to accumulation of glycosaminoglycans (GAGs) in many tissues, including the brain.

We are also working on 3D cell models for recapitulation of tumor – macrophage crosstalk in carcinomas. We have shown that in our 3D-3-cultures (co-cultures of tumor cell spheroids, fibroblasts and monocytes) features of immunosuppressive cancer microenvironments are recapitulated. There is accumulation of cytokines, ECM and metalloproteinases, with infiltration of macrophages in the tumor mass and trans-polarization into M2-like phenotypes. Challenging of the system with therapeutic compounds induced modulation of the M2-like phenotype. We are now applying the 3D-3 culture model to depict tumor-associated macrophage phenotypes associated with different subtypes of breast cancer.