Contextual Control of Adipose-Derived Stem Cell Function: Implications for Engineered Tumor Models

Adipose-derived stem cells (ASCs) are multipotent and, thus, are an attractive cell source for tissue engineering and regenerative medicine. However, ASCs can also differentiate into myofibroblasts, a cell type known to support tumorigenesis, yet the mechanisms underlying the myofibroblastic differentiation of ASCs and the resulting consequences on tumor pathogenesis are not well understood. This knowledge deficit is due, in part, to a lack of 3D culture models that capture the biological and physical heterogeneity of the microenvironment that influences ASC fate under both physiological and pathological conditions. Advanced biomanufacturing strategies offer new opportunities toward the generation of in vivo-like 3D culture environments that can help study how some of these conditions regulate ASC fate. This review discusses the protumorigenic plasticity of ASCs in the tumor microenvironment as well as other disease contexts (e.g., obesity and aging) and highlights advanced biomanufacturing technologies that could be used to integrate stromal parameters into the next generation of engineered 3D tumor models. Such models will enable new insights into ASC-dependent microenvironmental aspects contributing to tumor initiation and progression that may ultimately be targeted for improved anticancer therapies.