The chapter discusses the properties and significance of marrow stromal stem cells (MSCs), which were first identified in 1968 by Friedenstein and colleagues. MSCs are multipotent cells found in the bone marrow stroma that can differentiate into various connective tissues, including cartilage, bone, and adipose tissue. The physiological relevance of MSCs is demonstrated through in vivo transplantation experiments, where they generate chimeric ossicles that exhibit both donor and host-derived tissues. These cells retain their multipotentiality even after expansion in culture, and their differentiation outcomes can vary, depending on experimental conditions. The chapter also explores the ontogeny of MSCs, their role in skeletal development, and their plasticity in shifting between different phenotypes. It highlights the importance of the transcription factor cbfa1 in osteogenic differentiation and the development of the marrow stroma. The plasticity of MSCs is further discussed, noting that they can adopt alternative phenotypes in both in vitro and in vivo settings, such as reverting from adipocytic to osteogenic cells. The clinical potential of MSCs is examined, including their use in reconstructing localized skeletal defects, gene therapy, and treating systemic bone diseases. However, the chapter cautions that systemic transplantation of MSCs is unlikely due to their differences from hematopoietic stem cells (HSCs) and the challenges in ensuring their engraftment and function in the recipient's body. Despite these limitations, the chapter concludes by emphasizing the ongoing research and potential future applications of MSCs in medicine.The chapter discusses the properties and significance of marrow stromal stem cells (MSCs), which were first identified in 1968 by Friedenstein and colleagues. MSCs are multipotent cells found in the bone marrow stroma that can differentiate into various connective tissues, including cartilage, bone, and adipose tissue. The physiological relevance of MSCs is demonstrated through in vivo transplantation experiments, where they generate chimeric ossicles that exhibit both donor and host-derived tissues. These cells retain their multipotentiality even after expansion in culture, and their differentiation outcomes can vary, depending on experimental conditions. The chapter also explores the ontogeny of MSCs, their role in skeletal development, and their plasticity in shifting between different phenotypes. It highlights the importance of the transcription factor cbfa1 in osteogenic differentiation and the development of the marrow stroma. The plasticity of MSCs is further discussed, noting that they can adopt alternative phenotypes in both in vitro and in vivo settings, such as reverting from adipocytic to osteogenic cells. The clinical potential of MSCs is examined, including their use in reconstructing localized skeletal defects, gene therapy, and treating systemic bone diseases. However, the chapter cautions that systemic transplantation of MSCs is unlikely due to their differences from hematopoietic stem cells (HSCs) and the challenges in ensuring their engraftment and function in the recipient's body. Despite these limitations, the chapter concludes by emphasizing the ongoing research and potential future applications of MSCs in medicine.