Extracellular Vesicles from Embryonic Stem Cells Make Mesenchymal Stem Cells More Effective in Therapy

Mesenchymal stem cell (MSC) is a category so broad as to be near meaningless, but many varieties are widely used for therapeutic purposes. MSCs are taken from any one of a variety of sources, expanded in culture, and introduced to the patient. Researchers here show that applying extracellular vesicles from embryonic stem cells to the cultured MSCs reduces the usual issues that arise when expanding cells in culture, such as senescence, and improves the effectiveness of MSCs as a therapy when tested in mice. On a practical basis, one would imagine that induced pluripotent stem cells would serve just as well as a source of extracellular vesicles with this capability.

Mesenchymal stem cells (MSCs), derived from several kinds of tissues such as placenta, umbilical cord, bone marrow, and adipose tissue, are multipotent stem cells that can differentiate into many cell types. MSCs have been recognized as important candidates for the treatment of many degenerative diseases or injuries. Furthermore, MSCs can be expanded by continuously passage in vitro, to obtain a sufficient number of cells that can be used for clinical applications. Along with the continuous passage in vitro, MSCs exhibit the senescence-associated features, including enlarged morphology, irreversible growth arrest, enhanced SA-β-gal activity, decreased stemness of stem cells, increased cell apoptosis and DNA damage foci, and telomere attrition.

For senescent MSCs, the characteristics of stem cell are lost, and their therapeutic effects are limited. Therefore, researchers attempt to find a better way to block the cellular senescence. Mouse embryonic stem (ES) cells, derived from the blastocyst stage embryos, are distinguished by their ability to self-renew and differentiate into all cell types. The major barriers to the possible transplantation of ES cells into patients are immune rejection and the risk of forming tumors. It has been reported that conditioned medium from ES cells (ES-CM) has beneficial effects on cell proliferation and tissue regeneration via the factors secreted from ES cells.

Recently studies suggested that extracellular vesicles (EVs), which are biological particles released by many cell types, could be considered for therapeutic utility. The EVs transfer proteins and nucleic acids between cells and play an important role in the target cells. Moreover, EVs isolated from various types of stem cells have different properties such as anti-apoptosis, pro-angiogenesis, and anti-fibrosis. In this study, we explored the effects of EVs derived from ES cells (ES-EVs) on the senescent MSCs. Our results indicated that ES-EVs rejuvenated the senescent MSCs and enhanced their therapeutic effects in a mouse cutaneous wound model.

Link: https://doi.org/10.7150/thno.35305


I'd speculate that this might have applications in other therapies where cells are expanded in vitro such as preventing anergy when expanding CAR T cells for cancer therapy.

Posted by: jimofoz at November 8th, 2019 5:01 AM
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