Effects of the hypoxia, inflammation, and 3D culture on MSC in terms of expression and secretion of molecules of interest for cell therapy. a) Hypoxia activates the HIF and the NF-kappa β; increases the expression of several growth factors (inside the square), it also induces IDO activity and enhances stemness (Oct-4 and Rex-1). Also, the hypoxia pre-conditioned MSC, favor the activation of caspase 3, Bcl-2, MTP-2, TGF- β1 on target cells improving apoptosis resistance; improve regenerative capacity of muscle and endothelial cells. b) Inflammation induced by INF-γ increases the expression of anti-inflammatory and regenerative molecules (in the square) and, through TNF-α enhances the production of VEGF and BMP-2 which favor formation of new vessels and osteoblasts respectively. Also MSC exposed to LPS are able to encapsulate mitochondria and deliver them to other cells. c) 3D culture methods such as microcarriers or spheroids induce the production of TSG-6 and increases PGE2 secretion. Besides, it also favor the secretion of antiapoptotic and anticancer molecules (in the square). Further, MSCs obtained from 3D configurations, inhibit the expression of inflammatory and cancer related molecules in target cells.