Our laboratory conducts research primarily focused on induced pluripotent stem cells (iPSCs) and regenerative medicine. In particular, we are developing technologies to induce chondrogenic differentiation by faithfully recapitulating human developmental processes. iPSCs are artificially generated pluripotent stem cells with the potential to serve as a transformative therapeutic modality for cartilage-related disorders, including osteoarthritis of the knee. By leveraging iPSC-based strategies, it is anticipated that symptoms such as joint pain and restricted mobility can be alleviated, thereby enabling patients to lead more active, comfortable, and higher-quality daily lives.
Therapeutic potential of developmentally inspired approaches
Our approach is centered on promoting efficient differentiation of iPSCs into cartilage by mimicking key aspects of human embryonic development. If successful, this strategy would enable the regeneration and repair of articular cartilage in patients with knee osteoarthritis. As a consequence, joint function is expected to improve, allowing patients to move without pain and regain comfort and enjoyment in their daily activities.
Rationale for pursuing this research
The principal investigator, Dr. Takarada, was originally trained at Kanazawa University prior to establishing an independent laboratory, where he engaged in the analysis of skeletal development using genetically engineered mouse models. His work included skeletal preparations, histological examinations, and molecular and cellular biological analyses using cultured cells. Through these studies, he became deeply impressed by the elegance and precision with which life is generated from a fertilized egg. Upon obtaining an independent position in a medical school setting, he sought to apply the knowledge and expertise he had accumulated, leading to the establishment of a research program focused on human pluripotent stem cells, including iPSCs.
Limb bud mesenchymal cells (LBM) are derived from the lateral plate mesoderm and possess the capacity to differentiate into a wide range of cell types that constitute the limb skeleton, including chondrocytes, osteoblasts, tendon and ligament cells, and dermal fibroblasts. By utilizing LBM derived from human pluripotent stem cells, we aim to elucidate the hierarchical branching points within stem and progenitor cell differentiation, the signaling cues that operate at these junctures, the resulting intracellular changes, and the temporal and spatial coordination through which diverse cell types are generated to construct the human skeletal system.
Research achievements and future perspectives
In 2021, we successfully developed a method to induce and expand limb bud mesenchymal cells (LBM)—the cellular population that constitutes the primordia of the limbs (upper and lower extremities)—and reported this achievement in Nature Biomedical Engineering (2021).
Through research that integrates iPSC technology with regenerative medicine, our laboratory aims to achieve groundbreaking advances in the treatment of cartilage-related disorders, such as knee osteoarthritis. From the perspective of creating novel medical therapies, LBM can be utilized as a new cellular source for regenerative approaches targeting the musculoskeletal system, including cartilage. In addition, by generating iPSCs from patients with skeletal disorders, it becomes possible to recapitulate disease pathophysiology in vitro, thereby facilitating drug discovery and development. Furthermore, because this technology enables the controlled induction of various human limb constituent cell types by mimicking developmental processes, its combination with genome-editing techniques offers a powerful platform to investigate the origins of bone and soft-tissue tumors arising in the limbs and to translate these insights into innovative cancer therapies.