Mesenchymal stem cell secreted vesicles provide novel opportunities in (stem) cell-free therapy

Abstract

Mesenchymal stem cells (MSCs) are adult multipotent cells that give rise to various cell types of the mesodermal germ layer. MSCs are of great interest in the field of regenerative medicine and cancer therapy because of their unique ability to home to damaged and cancerous tissue. These cells also regulate the immune response and contribute to reparative processes in different pathological conditions, including musculoskeletal and cardiovascular diseases. The use of MSCs for tissue repair was initially based on the hypothesis that these cells home to and differentiate within the injured tissue into specialized cells. However, it now appears that only a small proportion of transplanted MSCs actually integrate and survive in host tissues. Thus, the predominant mechanism by which MSCs participate in tissue repair seems to be related to their paracrine activity. Indeed, MSCs provide the microenvironment with a multitude of trophic and survival signals including growth factors and cytokines. Recent discoveries suggest that lipid microvesicles released by MSCs may also be important in the physiological function of these cells. Over the past few years the biological relevance of micro- and nano-vesicles released by cells in intercellular communication has been established. Alongside the conventional mediators of cell secretome, these sophisticated nanovesicles transfer proteins, lipids and, most importantly, various forms of RNAs to neighboring cells, thereby mediating a variety of biological responses. The physiological role of MSC-derived vesicles (MSC-MVs) is currently not well understood. Nevertheless, encouraging results indicate that MSC-MVs have similar protective and reparative properties as their cellular counterparts in tissue repair and possibly anti-cancer therapy. Thus, MSC-MVs represent a promising opportunity to develop novel cell-free therapy approaches that might overcome the obstacles and risks associated with the use of native or engineered stem cells.

Increasing of blastocyst rate and gene expression in co-culture of bovine embryos with adult adipose tissue-derived mesenchymal stem cells

“…Thus, a stem cell-free model may be the desirable approach for cell therapy in the future once authors are showing positive effects of using only stem cell-conditioned medium for therapies which could avoid, for example, the risk of erratic cell divisions (tumors) in patients and also cell membrane-related antigen reactions giving opportunity to interspecies therapy, for example [14,15,17].…”

“…Growth factors, cytokines, and microRNAs (enclosed in exosomal microvesicles) have been listed as probable effector molecules responsible for the positive results achieved in many cell therapy studies, rather than a direct contribution to tissue regeneration from stem cell differentiation [14,16,17]. Exosomes are small vesicles (60 to 200 nm) produced by a variety of cell types, including MSCs, that may fuse with the plasma membrane of target cells to deliver mRNA, microRNAs, and even proteins [27][28][29][30].…”

“…These studies have been primarily motivated by the fact that stem cells have the ability to secrete a variety of substances such as cytokines, growth factors, and even microRNAs, which are collectively capable of modulating the surrounding microenvironment [14][15][16][17]. For instance, in wound repair studies, evidence suggests that most of the therapeutic effects of transferred mesenchymal stem cells may be due to the release of soluble factors that regulate local cellular responses to cutaneous injury; this is further supported by the fact that stem cellconditioned medium is able to promote tissue repair [18].…”

Modularized Extracellular Vesicles: The Dawn of Prospective Personalized and Precision Medicine

“…In recent years, the therapeutic properties of MSCs have been considered to be due to the therapeutic effect of the secretome, especially EVs 80. A number of preclinical studies, including of ischemia, neurodegenerative diseases, fibrotic liver, and acute kidney injury, have explored the potential efficacy of MSC‐derived EVs in tissue regeneration 81, 82, 83. In addition, the immune‐suppressive capacity of MSC‐derived EVs, as a result of the proteins and RNAs they transport, has been recognized to regulate immunity via the release of anti‐inflammatory cytokines or modulation of the Toll‐like receptor signaling pathway 84…”

Cardiovascular Diseases: Recent Developments in Regenerative Medicine

“…The MSCs along with other factors, secrete exosomes which are vesicles containing biological molecules primarily proteins, mRNA, microRNA and lipid [32]. Exosomes play vital role in cell-cell interaction and mediating bidirectional exchange of material.…”