Preactivation of Human MSCs with TNF-α Enhances Tumor-Suppressive Activity

Abstract

Mesenchymal stem/stromal cells (MSCs) can either suppress or promote tumors. We found previously that incubation of human bone marrow MSCs (hMSCs) with TNF-α upregulated multiple genes including TRAIL, which has cancer apoptotic activity. Here, we show that weekly infusions into mice of hMSCs preactivated with TNF-α inhibited the progression of lung tumors formed from MDA-MB-231 breast cancer cells (MDA). In coculture, preactivated hMSCs induced apoptosis in MDA and several other TRAIL-sensitive cancer cell lines. TRAIL was further upregulated by apoptotic MDA cells in a TLR3-dependent manner; this feedforward cycle increased MDA cell apoptosis, and the chemotherapeutic drug doxorubicin had a synergistic effect. Also, activated hMSCs secreted DKK3 to suppress MDA cell cycling, leading to a decrease in β-catenin and cyclin D1/D3 and an increase in p21. Thus, culturing hMSCs with TNF-α enhances their tumor-suppressive properties and may represent a useful strategy to develop hMSC-based approaches for the treatment of cancer.

In Vivo Photoacoustic Imaging of Brain Injury and Rehabilitation by High‐Efficient Near‐Infrared Dye Labeled Mesenchymal Stem Cells with Enhanced Brain Barrier Permeability

“…All mice were sacrificed and main organs were harvested for the ex vivo fluorescence imaging. From Figure 6C, a lot transplanted stem cells were entrapped by organs such as lung and liver, which was also previously observed during intravenous administration 19, 31. However, a great number of BMSCs still migrated to the brain for therapeutics.…”

Anti-apoptotic Effects of Human Wharton's Jelly-derived Mesenchymal Stem Cells on Skeletal Muscle Cells Mediated via Secretion of XCL1

“…For example, the paracrine action of human MSC has been demonstrated to prevent cell death and induce proliferation of endogenous progenitor cells. [17][18][19][20][21] Therefore, human MSCs have been described as injury drug store. 22,23 Lately, numerous paracrine factors have been identified through proteomic approaches.…”

Should Publications on Mesenchymal Stem/Progenitor Cells Include In-Process Data on the Preparation of the Cells?

“…Some strategies, particularly protocols to preactivate MSCs in culture with Toll-like receptor ligands or other stimulants, show great promise as efficacy tests for the cells [25][26][27]. New technologies for epigenetic analyses of cells could provide important information about MSCs, but the large amounts of data generated are still difficult to interpret [29].…”