Umbilical Cord Blood-Derived Mesenchymal Stem Cells Inhibit, But Adipose Tissue-Derived Mesenchymal Stem Cells Promote, Glioblastoma Multiforme Proliferation

Abstract

Mesenchymal stem cells (MSCs) possess self-renewal and multipotential differentiation abilities, and they are thought to be one of the most reliable stem cell sources for a variety of cell therapies. Recently, cell therapy using MSCs has been studied as a novel therapeutic approach for cancers that show refractory progress and poor prognosis. MSCs from different tissues have different properties. However, the effect of different MSC properties on their application in anticancer therapies has not been thoroughly investigated. In this study, to characterize the anticancer therapeutic application of MSCs from different sources, we established two different kinds of human MSCs: umbilical cord blood-derived MSCs (UCB-MSCs) and adipose-tissue-derived MSCs (AT-MSCs). We used these MSCs in a coculture assay with primary glioblastoma multiforme (GBM) cells to analyze how MSCs from different sources can inhibit GBM growth. We found that UCB-MSCs inhibited GBM growth and caused apoptosis, but AT-MSCs promoted GBM growth. Terminal deoxynucleotidyl transferase-mediated biotinylated UTP nick-end labeling assay clearly demonstrated that UCB-MSCs promoted apoptosis of GBM via tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). TRAIL was expressed more highly by UCBMSCs than by AT-MSCs. Higher mRNA expression levels of angiogenic factors (vascular endothelial growth factor, angiopoietin 1, platelet-derived growth factor, and insulin-like growth factor) and stromal-derived factor-1 (SDF-1/CXCL12) were observed in AT-MSCs, and highly vascularized tumors were developed when ATMSCs and GBM were cotransplanted. Importantly, CXCL12 inhibited TRAIL activation of the apoptotic pathway in GBM, suggesting that AT-MSCs may support GBM development in vivo by at least two distinct mechanisms-promoting angiogenesis and inhibiting apoptosis. The opposite effects of AT-MSCs and UCBMSCs on GBM clearly demonstrate that differences must be considered when choosing a stem cell source for safety in clinical application.

Adipose-Derived Stems Cells and Their Role in Human Cancer Development, Growth, Progression, and Metastasis: A Systematic Review

“…In addition, Zhao and colleagues (57) reported that ASCs chemoattract endothelial cells by a VEGFdependent method. Jeon and colleagues (58) showed that the lysophosphatidic acid (LPA)-LPA1 signaling pathway played a key role in ASC differentiation and VEGF-mediated angiogenesis, Akimoto and colleagues (59) illustrated that ASCs may support glioblastoma multiforme by promoting angiogenesis, and Klopp and colleagues (60) suggested that through expressing various, specific factors, omental ASCs increase tumor vascularization in endometrial cancer.…”

Perspectives in Engineered Mesenchymal Stem/Stromal Cells Based Anti- Cancer Drug Delivery Systems

“…But the anti-cancer properties of MSCs in humans are controversial because of still incomplete and limited human studies performed on small number of patients. The proposed use of MSCs in cancer therapies provoke strong disagreement in scientific community, due to opposite results for MSC promotion of tumor vascularization, promotion of cancer progression and the invasive tendency of tumors previously reported [28,[120][121][122]. In this contest, Li et al, 2011, inform about the dual role of human MSCs in tumor cell growth in vitro and in vivo.…”

“…There is still no confirmation of this hypothesis, and investigations are still in progress as many authors have described cells from the microenvironment which exhibit several differences with their parent cells. In one study [28]. Isolated primary glioblastoma multiforme (GBM) cells are co-cultured with MSCs and their characteristics are analyzed with cotransplantation assays.…”

“…In general, results leading to the proposal of two major elements are likely to be correlated with the significant impact on cancer development. The first element is bidirectional cell communication, and the second one is the possibility of suppressive outcomes over the immune system which at the same time make tumor genesis possible [16,[27][28][29]. Almost certainly, this bidirectional cellular communication is a crucial stage in tumor progression (Fig.…”

Stem Cell Therapy for Brain Tumors

“…MSCs have been extracted from several adult human tissues including the connective tissues of all human organs, the bone marrow (BM), skeletal muscle, synovium, dental pulp, and adipose tissues [29][30][31][32][33]. MSCs can also be harvested from fetal tissues such as umbilical cord blood, placenta, amniotic membranes, and amniotic fluid [31,[33][34][35][36][37][38][39].…”