Effects of 3D Cell Culture on the Cell Fate Decisions of Mesenchymal Stromal/Stem Cells

In vivo, all stem cells reside within distinct and defined microenvironments referred to as stem cell niches. Complex interactions between stem cells and their niche tightly regulate cell fate decisions. This affects live/death decisions, cellular senescence, and cell differentiation. Therefore, removing mesenchymal stromal/stem cells (MSCs) from their niche and cultivation within conventional flat, two-dimensional (2D) cell culture systems affects their cell fate and therefore also their regenerative potential. Nevertheless, routine MSC culture for research and therapy is still conducted in 2D. Three-dimensional (3D) cell culture is a state-of-the-art technology allowing expanding and differentiating MSCs under more physiological conditions. This chapter will summarize current understanding of the impact of 3D cell culture on fundamental properties of MSCs including their proliferation, viability, cellular senescence, and differentiation. Furthermore, effects of 3D cell culture on the immunomodulatory and anti-inflammatory potential of MSCs will be evaluated.