Anti-Tumor Effects of Exosomes Derived from Drug-Incubated Permanently Growing Human MSC

Abstract

Similar to growth-limited human primary cultures of mesenchymal stroma/stem-like cells (MSC), the continuously proliferating human MSC544 cell line produced extracellular vesicles as characterized by expression of the tetraspanin molecules CD9, CD63, and CD81. Release of these particles was predominantly detectable during continuous cell growth of MSC544 in contrast to confluency-mediated transient growth arrest. For therapeutic use, these particles were isolated from proliferating MSC544 after taxol treatment and applied to different cancer cell cultures. A pronounced cytotoxicity of lung, ovarian, and breast cancer cells was observed primarily with taxol-loaded exosomes, similar to the effects displayed by application of taxol substance. While these findings suggested pronounced cancer cell targeting of MSC544 exosomes, a tumor therapeutic approach was performed using a mouse in vivo breast cancer model. Thus, intravenous injection of taxol-loaded MSC544 exosomes displayed superior tumor-reducing capabilities as compared to application of taxol exosomes by oral gavage. To broaden this therapeutic spectrum, epirubicin was applied to MSC544, and the derived exosomes likewise exhibited significant cytotoxic effects in different cancer cell cultures. These findings suggest an unlimited source for large-scale exosome production with reproducible quality to enable variable drug targeting of tumors or other diseases.

The Intimate Relationship among EMT, MET and TME: A T(ransdifferentiation) E(nhancing) M(ix) to Be Exploited for Therapeutic Purposes

“…Furthermore, transition from the highly tumorigenic E/M state to a less-tumorigenic fully mesenchymal phenotype, which can be achieved i.e., by forced expression of Zeb1, is accompanied by a switch from canonical to non-canonical Wnt signaling. Identifying the central regulators of the various phenotypic states may prove useful in designing new therapeutic approaches [79,80] that function by shifting cancer cells between distinct states along the E/M spectrum [66] (Figure 2).…”

Effect of SSRI exposure on the proliferation rate and glucose uptake in breast and ovary cancer cell lines

“…Figs. S1 and S2 ) as described previously 32 – 34 .

Figure 1 SSRI treatment or 5-HT exposure marginally impact cell proliferation of breast cancer cell lines.

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Roles of Mesenchymal Stem Cell-Derived Exosomes in Cancer Development and Targeted Therapy

“…Taxol is a widely used chemotherapy drug. Melzer et al [76] treated MSC544 cells with Taxol, and then exosomes were isolated using a serum-free MSC544 medium under continuous centrifugation conditions after 24 h. Human MDA-hyb1 triple-negative breast cancer cells were injected subcutaneously to induce subcutaneous tumors in 15 NOD/SCID mice. Subsequently, Taxolloaded MSC544 exosomes were injected intravenously into tumor-bearing mice.…”