Multipotent mesenchymal stromal cells: clinical applications and cancer modeling.
ABSTRACT The recognition of the therapeutic potential of Multipotent Mesenchymal Stromal Cells (MSCs) is one of the most exciting recent advances in cell therapy. In just ten years, since the description of the multilineage potential of MSCs by Pittenger et al in 1999 until now, MSCs are being used in more than 150 clinical trials as therapeutic agents. The potential of these cells for cell-based therapies relies on several key properties: (1) their capacity to differentiate into several cell lineages; (2) their lack of immunogenicity and their immunomodulatory properties; (3) their ex vivo expansion potential; (4) their ability to secrete soluble factors which regulate crucial biological functions such as proliferation and differentiation over a broad spectrum of target cells; and (5) their ability to home to damaged tissues and tumor sites. Based on these properties MSCs are being exploited worldwide for a wide range of potential clinical applications including cell replacement strategies, treatment of graft-versus-host disease, autoimmune diseases and rejection after solid organ transplantation as well as their use as vehicles to deliver anti-cancer therapies. Importantly, the low inherent immunogenicity of MSCs means that they could be used not only for autologous but also for allogeneic cell therapies. In addition, increasing evidence has revealed a complex relationship between MSCs and cancer. Thus, solid evidence has placed MSCs transformed with specific mutations as the most likely cell of origin for certain sarcomas, and MSCs have been reported to both, inhibit or promote tumor growth depending on yet undefined conditions. Here we will thoroughly discuss the different potential clinical applications of MSC as well as the role of MSCs on sarcomagenesis and the control of tumor growth.