Generation of mesenchymal stem-like cells for producing extracellular vesicles

Abstract

Mesenchymal stem cells (MSCs) are multipotent progenitor cells with therapeutic potential against autoimmune diseases, inflammation, ischemia, and metabolic disorders. Contrary to the previous conceptions, recent studies have revealed that the tissue repair and immunomodulatory functions of MSCs are largely attributed to their secretome, rather than their potential to differentiate into desired cell types. The composition of MSC secretome encompasses cytokines and growth factors, in addition to the cell-derived structures known as extracellular vesicles (EVs). EVs are membrane-enclosed nanoparticles that are capable of delivering biomolecules, and it is now believed that MSC-derived EVs are the major players that induce biological changes in the target tissues. Based on these EVs' characteristics, the potential of EVs derived from MSC (MSC-EV) in terms of tissue regeneration and immune modulation has grown during the last decade. However, the use of MSCs for producing sufficient amount of EVs has not been satisfactory due to limitations in the cell growth and large variations among the donor cell types. In this regard, pluripotent stem cells (PSCs)-derived MSC-like cells, which can be robustly induced and expanded in vitro, have emerged as more accessible cell source that can overcome current limitations of using MSCs for EV production. In this review, we have highlighted the methods of generating MSC-like cells from PSCs and their therapeutic outcome in preclinical studies. Finally, we have also discussed future requirements for making this cell-free therapy clinically feasible.

Keywords: Exosomes; Extracellular vesicles; Mesenchymal stem cells; Preclinical studies.

Figure 1

Multifaceted origin and application of mesenchymal stem cells. Mesenchymal stem cells (MSCs) can be isolated directly from various donor tissue types including adipose tissue, bone marrow or umbilical cord. MSC-like cells (induced MSC; iMSC) can be induced from pluripotent stem cells (iPSC, induced pluripotent stem cell). MSC/iMSC can be differentiated to multiple cells types including adipocytes, chondrocytes or osteocytes. The secreted products from MSC/iMSC such as extracellular vesicles, growth factors and cytokines also play essential role in their regenerative function. MSC: Mesenchymal stem cell; iMSC: Induced mesenchymal stem cell; ESC: Embryonic stem cell.