Extracellular vesicles (EVs) are cell-derived nanostructures that mediate intercellular communication by delivering complex signals in normal tissues and cancer. The cellular coordination required for tumor development and maintenance is mediated, in part, through EV transport of molecular cargo to resident and distant cells. Most studies on EV-mediated signaling have been performed in two-dimensional (2D) monolayer cell cultures, largely because of their simplicity and high-throughput screening capacity. Three-dimensional (3D) cell cultures can be used to study cell-to-cell and cell-to-matrix interactions, enabling the study of EV-mediated cellular communication. 3D cultures may best model the role of EVs in formation of the tumor microenvironment (TME) and cancer cell-stromal interactions that sustain tumor growth. In this review, we discuss EV biology in 3D culture correlates of the TME. This includes EV communication between cell types of the TME, differences in EV biogenesis and signaling associated with differing scaffold choices and in scaffold-free 3D cultures and cultivation of the premetastatic niche. An understanding of EV biogenesis and signaling within a 3D TME will improve culture correlates of oncogenesis, enable molecular control of the TME and aid development of drug delivery tools based on EV-mediated signaling.

Extracellular vesicles (EVs) are essential mediators of intercellular communication that can affect physiological and pathological conditions by transferring nucleic acids and proteins. In this study, we investigate EV-mediated intercellular communication using both in-silico and in-vitro models. We isolated EVs from human heart organoids (HHO); these systems reproduce many of the structural and functional aspects of the early developing human heart. These HHOs are grown under high glucose and high insulin conditions to model pregestational diabetes, a maternal disease associated with congenital heart defects. Using the diabetic HHO model, we hypothesized that EV miscommunication may be, in part, a cause of congenital heart defects associated with pregestational diabetes. EV characterization was done through Western blotting and nanoparticle tracking analysis (NTA). The anomalous diffusion and the biodistribution of EVs in a cardiac extracellular matrix (ECM) were modeled using 3-dimensional partial differential equations, and the model was verified by particle-based simulations. Our in-vitro research identified Alix and Flotinin-1 proteins as markers of EVs from diabetic HHO, and NTA revealed that EVs with a diameter of 105 nm are detected most frequently. Our in-silico research demonstrates that EV concentrations in the cardiac ECM exhibit varying patterns based on our NTA characterization. Our findings can provide a foundation for future EV-mediated treatment methods and improve our understanding of intercellular communication in pregestational diabetes and heart development.

Social determinants of health (SDoH), including economic stability, education, healthcare access, neighborhood environment, and community context, play a critical role in shaping health outcomes. Telehealth, defined as the use of digital and telecommunications technologies to deliver healthcare remotely, presents both opportunities and risks for equity. It can reduce barriers such as transportation costs and distance, yet it may also deepen disparities among populations with limited digital access or literacy. This review highlights lessons from selected global and U.S. telehealth programs to examine how SDoH influence adoption and outcomes. Key challenges include digital literacy gaps, privacy concerns, cultural preferences for in-person care, provider training deficits, infrastructure limitations, and reimbursement inconsistencies. Potential solutions include policy reforms, broadband expansion, digital literacy initiatives, and community-centered approaches. By framing telehealth through an SDoH lens, this review contributes to the literature by clarifying strategies that can advance more equitable and sustainable implementation.