An In Vitro Comparison of Anti-Tumoral Potential of Wharton’s Jelly and Bone Marrow Mesenchymal Stem Cells Exhibited by Cell Cycle Arrest in Glioma Cells (U87MG)

Abstract

The therapeutic potential of mesenchymal stem cells (MSCs) for various malignancies is currently under investigation due to their unique properties. However, many discrepancies regarding their anti-tumoral or pro-tumoral properties have raised uncertainty about their application for anti-cancer therapies. To investigate, if the anti-tumoral or pro-tumoral properties are subjective to the type of MSCs under different experimental conditions we set out these experiments. Three treatments namely cell lysates (CL), serum-free conditioned media and FBS conditioned media (FBSCM) from each of Wharton’s Jelly MSCs and Bone Marrow-MSCs were applied to evaluate the anti-tumoral or pro-tumoral effect on the glioma cells (U87MG). The functional analysis included; Morphological evaluation, proliferation and migration potential, cell cycle analysis, and apoptosis for glioma cells. The fibroblast cell line was added to investigate the stimulatory or inhibitory effect of treatments on the proliferation of the normal cell. We found that cell lysates induced a generalized inhibitory effect on the proliferation of the glioma cells and the fibroblasts from both types of MSCs. Similarly, both types of conditioned media from two types of MSCs exerted the same inhibitory effect on the proliferation of the glioma cells. However, the effect of two types of conditioned media on the proliferation of fibroblasts was stimulatory from BM-MSCs and variable from WJ-MSCs. Moreover, all three treatments exerted a likewise inhibitory effect on the migration potential of the glioma cells. Furthermore, we found that the cell cycle was arrested significantly at the G1 phase after treating cells with conditioned media which may have led to inhibit the proliferative and migratory abilities of the glioma cells (U87MG). We conclude that cell extracts of MSCs in the form of secretome can induce specific anti-tumoral properties in serum-free conditions for the glioma cells particularly the WJ-MSCs and the effect is mediated by the cell cycle arrest at the G1 phase.

The Dual Role of Mesenchymal Stromal Cells and Their Extracellular Vesicles in Carcinogenesis

“…In addition, MSCs integrated with tumor cells and had a significant inhibitory effect on the proliferation of malignant pleural mesothelioma cells [ 67 ]. Aslam et al showed that MSC lysates (Wharton’s Jelly and bone marrow) induced a general inhibitory effect on the proliferation of glioma cells and fibroblasts [ 68 ].…”

Cell-Based Therapy for the Treatment of Glioblastoma: An Update from Preclinical to Clinical Studies

“…The MSC-derived secretome can also exhibit cell cycle arrest in GB cells [ 95 ]. Moreover, cytotoxic cell death can be achieved by MSCs with expressed tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL).…”

Application of Mesenchymal Stem Cells in Targeted Delivery to the Brain: Potential and Challenges of the Extracellular Vesicle-Based Approach for Brain Tumor Treatment

“…Earlier findings about anti-tumor properties of MSC secretomes were done using conditioned medium (CM) of MSC cultures to treat cancer cells. There are reports on the inhibitory effects of UC-MSC CM on C6 glioma cell growth [ 154 ], inhibitory effects of AT-MSC and UC-MSC CM on U251 glioma cell proliferation, migration, and invasion [ 155 ], stimulatory effects of BM-MSC and UC-MSC CM on GBM stem-like cells’ response to temozolomide (TMZ) and cell-cycle arrest [ 156 ], and stimulatory effects of BM-MSC and WJ-MSC CM on U87 cell cell-cycle arrest [ 157 ]. A more recent study specifically used the exosomes isolated from CM of UC-MSCs, which expressed an inhibitory effect on U87 cell growth [ 158 ].…”