Strategies to capitalize on cell spheroid therapeutic potential for tissue repair and disease modeling.

Cell therapies offer a tailorable, personalized treatment for use in tissue engineering to address defects arising from trauma, inefficient wound repair, or congenital malformation. However, most cell therapies have achieved limited success to date. Typically injected in solution as monodispersed cells, transplanted cells exhibit rapid cell death or insufficient retention at the site, thereby limiting their intended effects to only a few days. Spheroids, which are dense, three-dimensional (3D) aggregates of cells, enhance the beneficial effects of cell therapies by increasing and prolonging cell-cell and cell-matrix signaling. The use of spheroids is currently under investigation for many cell types. Among cells under evaluation, spheroids formed of mesenchymal stromal cells (MSCs) are particularly promising. MSC spheroids not only exhibit increased cell survival and retained differentiation, but they also secrete a potent secretome that promotes angiogenesis, reduces inflammation, and attracts endogenous host cells to promote tissue regeneration and repair. However, the clinical translation of spheroids has lagged behind promising preclinical outcomes due to hurdles in their formation, instruction, and use that have yet to be overcome. This review will describe the current state of preclinical spheroid research and highlight two key examples of spheroid use in clinically relevant disease modeling. It will highlight techniques used to instruct the phenotype and function of spheroids, describe current limitations to their use, and offer suggestions for the effective translation of cell spheroids for therapeutic treatments.

In Vitro Models for Studying Transport Across Epithelial Tissue Barriers.

Epithelial barriers are the body's natural defense system to regulating passage from one domain to another. In our efforts to understand what can and cannot cross these barriers, models have emerged as a reductionist approach to rigorously study and investigate this question. In particular, in vitro tissue models have become prominent as there is an increased exploration of understanding biological molecular transport. Herein, we introduce the pertinent physiology, then discuss recent studies and approaches for building models of five epithelial tissues: skin, the gastrointestinal tract, the lungs, the blood-brain barrier, and the placenta. In particular, we evaluated literature from the past 5 years utilizing a tissue model to evaluate molecular transport. We then compare physiology of these tissues and discuss similarities in approaches, across tissues, to validate these models. We conclude with a summary of the approaches of growing interest across multiple tissues and an outlook on future steps to improve these models.