A peculiar molecular profile of umbilical cord-mesenchymal stromal cells drives their inhibitory effects on multiple myeloma cell growth and tumor progression.

Bone marrow-derived mesenchymal stromal cells (BM-MSCs) are under intensive investigation in preclinicalmodels of cytotherapies against cancer, including multiple myeloma (MM). However, the therapeutic use ofstromal progenitors holds critical safety concerns due to their potential MM-supporting activity in vivo. Here,we explored whether MSCs from sources other than BM, such as adipose tissue (AD-MSCs) and umbilical cord(UC-MSCs), affect MM cell growth in comparison to either normal (nBM-MSCs) or myelomatous marrowMSCs (MM-BM-MSCs). Results from both proliferation and clonogenic assays indicated that, in contrast tonBM- and MM-BM-MSCs, both AD and particularly UC-MSCs significantly inhibit MM cell clonogenicity andgrowth in vitro. Furthermore, when co-injected with UC-MSCs into mice, RPMI-8226 MM cells formedsmaller subcutaneous tumor masses, while peritumoral injections of the same MSC subtype significantlydelayed the tumor burden growing in subcutaneous plasmocytoma-bearing mice. Finally, both microarrays andELISA revealed different expression of several genes and soluble factors in UC-MSCs as compared with otherMSCs. Our data suggest that UC-MSCs have a distinct molecular profile that correlates with their intrinsic anti-MM activity and emphasize the UCs as ideal sources of MSCs for future cell-based therapies against MM.