Our lab focuses on tissue regeneration and tissue repair using cutting-edge tissue engineering and stem cell strategies. Currently, our tissues of interest include articular cartilage, bone, intervertebral disc, and meniscus. Engineering a tissue construct is initiated by seeding appropriate cells on biodegradable and biocompatible scaffolds. This step is followed by incubation in an environment with physical and chemical signals (imitating in vivo tissue regeneration and development) to stimulate construct differentiation into premature tissue for implantation. Adult stem cells, such as synovium-derived stem cells (SDSCs), bone marrow derived stem cells (BMSCs), and adipose stem cells (ASCs), have been demonstrated to play a key role in tissue engineering and regeneration. Adult stem cells have proliferation and multilineage differentiation capacities; however, traditional in vitro monolayer culture (2D) makes cells undergo an 'aging' process in which their morphology changes and their proliferative capacity decreases. It is believed that culturing conditions for adult stem cells need to be improved so that adult stem cells can maintain their stemness over time; this is one of the major challenges to be overcome for the advancement of regenerative medicine. Our lab developed a 3D nanostructured expansion system (in vitro stem cell niche) using extracellular matrix (ECM) deposited by adult stem cells. Stem cells expanded on ECM exhibited enhanced proliferation and chondrogenic differentiation capacities. Interestingly, this 3D expansion system also works for primary cells, such as articular chondrocytes and nucleus pulposus cells. Understanding the underlying mechanism and identifying the key component(s) responsible for this rejuvenation effect is important for this technique to be applicable in clinical regenerative medicine. Despite the fact that many mysteries still need to be solved, in vitro reconstruction of the stem cell niche may play a critical role in the next generation of tissue engineering and regenerative medicine.