A technical improvement enabling efficient and reproducible stem cell cultures is one of the most important aspects in stem cell research and cell-based therapy. For this purpose, researchers have used various cytokine cocktails and gene transfection techniques to proliferate stem cells. However, stem cell fate can reportedly be determined by physical stimuli such as gravity, electrical fields, and magnetic fields. In this regard, we have developed a novel technique utilizing a clinostat, a device capable of generating a controlled microgravity environment for robust maintenance of stem cell state. Here, we review our recent progress in expansion and differentiation of stem cells grown under simulated microgravity environment and their utility for transplantation in animal models of cartilage deficiency and neurotrauma.