Extracellular vesicles from bone marrow mesenchymal stem/stromal cells transport tumor regulatory microRNA, proteins, and metabolites

Abstract

Human mesenchymal stem/stromal cells (hMSCs) have been shown to support breast cancer cell proliferation and metastasis, partly through their secretome. hMSCs have a remarkable ability to survive for long periods under stress, and their secretome is tumor supportive. In this study, we have characterized the cargo of extracellular vesicular (EV) fraction (that is in the size range of 40-150nm) of serum deprived hMSCs (SD-MSCs). Next Generation Sequencing assays were used to identify small RNA secreted in the EVs, which indicated presence of tumor supportive miRNA. Further assays demonstrated the role of miRNA-21 and 34a as tumor supportive miRNAs. Next, proteomic assays revealed the presence of ≈150 different proteins, most of which are known tumor supportive factors such as PDGFR-β, TIMP-1, and TIMP-2. Lipidomic assays verified presence of bioactive lipids such as sphingomyelin. Furthermore, metabolite assays identified the presence of lactic acid and glutamic acid in EVs. The co-injection xenograft assays using MCF-7 breast cancer cells demonstrated the tumor supportive function of these EVs. To our knowledge this is the first comprehensive -omics based study that characterized the complex cargo of extracellular vesicles secreted by hMSCs and their role in supporting breast cancers.

Chromatographically isolated CD63 + CD81 + extracellular vesicles from mesenchymal stromal cells rescue cognitive impairments after TBI

“…Also, MSCs tend to home to injured tissues, and some of the EVs they produce may retain this homing ability. In addition, MSCs are an attractive source of EVs because of an unusual property of the cells: They can survive for weeks in culture with medium containing no protein or growth factors but continue to produce EVs (47)(48)(49)(50). During incubation of MSCs from bone marrow in α-MEM, the cultures underwent selection with survival of a subpopulation that expressed genes characteristic of embryonic cells (47).…”

“…During incubation of MSCs from bone marrow in α-MEM, the cultures underwent selection with survival of a subpopulation that expressed genes characteristic of embryonic cells (47). Pochampally and coworkers subsequently demonstrated that the MSCs incubated in α-MEM produced EVs, and they extensively characterized the EVs (48). They also demonstrated that the EVs supported tumor growth.…”

Exosomes in stroke pathogenesis and therapy

“…Exosomes transfer their cargo miRNAs to recipient cells (120,121) and MSC-derived exosomes contain more than 700 miRNAs that are bound to argonaute2 (AGO2), a component of the RNAinduced silencing complex (RISC) (122,123). The effect of engineered MSC-derived exosomes that carry elevated miRNAs on brain remodeling after stroke has been investigated in vitro and in vivo (118,119).…”

Microenvironment Signals and Mechanisms in the Regulation of Osteosarcoma

“…These metastatic OS cells secrete both an active soluble form and an exosome-encapsulated form of uPA to drive the migration or metastatic conversion of OS cells [139]. Other research demonstrated that exosomes secreted by human MSCs could exhibit antiapoptotic function or cell-protective function to increase OS survival under serum starvation conditions [140]. Exosomes may also be a neo-drug vector for OS treatment.…”