TGF-β and mesenchymal stromal cells in regenerative medicine, autoimmunity and cancer

Multipotent mesenchymal stromal cells (MSCs) represent a promising cell-based therapy in regenerative medicine and for the treatment of inflammatory/autoimmune diseases. Importantly, MSCs have emerged as an important contributor to the tumor stroma with both pro- and anti-tumorigenic effects. However, the successful translation of MSCs to the clinic and the prevention of their tumorigenic and metastatic effect require a greater understanding of factors controlling their proliferation, differentiation, migration and immunomodulation in vitro and in vivo. The transforming growth factor(TGF)-51, 2 and 3 are involved in almost every aspect of MSC function. The aim of this review is to highlight the roles that TGF-beta play in the biology and therapeutic applications of MSCs. We will discuss the how TGF-beta modulate MSC function as well as the paracrine effects of MSCderived TGF-beta on other cell types in the context of tissue regeneration, immune responses and cancer. Finally, taking all these aspects into consideration we discuss how modulation of TGF-beta signaling/production in MSCs could be of clinical interest.