[79] generated the new method of combining bone MSCs with the tumor-derived exosomes which was later confirmed to enhance MSCs’ antitumor activity

[79] generated the new method of combining bone MSCs with the tumor-derived exosomes which was later confirmed to enhance MSCs’ antitumor activity. of exosomes, providing an alternative way of developing strategies to cure diseases. 1. Introduction Regenerative medicine is designed to improve the regeneration of damaged, malfunctioning, and missing tissue and organs [1]. Mounting evidence supports that stem cell therapies may be promising in this field on the basis of potential therapeutic use of stem cells in damaged organs such as the myocardium after heart infarction, stroke, spinal cord injury, retina diseases, and damaged liver [2C4]. In addition, stem cells-based therapy may be a prospective GNGT1 way for diseases that are irreversible and incurable at present [5]. Specifically, regenerative medicine contains two goals: one is efficiently and safely transferring stem cells into hurt Anamorelin organs and tissues, which may replace the transplantation of the entire organ in the near future; the other is usually to develop strategies in order to improve the regenerative potential and function of adult stem cells residing in numerous organs [6]. In the last decades, numerous preclinical studies confirmed the therapeutic potentials of stem cells. Stem cells including embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs), and adult stem cells manifest respective merits and drawbacks. Some types of stem cells are being evaluated in clinical trials with encouraging results [7]. These stem cells such as mesenchymal stem cells (MSCs) are relatively safe, but therapeutic strategies avoiding direct use of living stem cells are more likely to provide a safer way to prevent disease progression. Although direct and indirect mechanisms such as growth factors and cytokines have accounted for the therapeutic effects, paracrine secretion seems to play a predominant role. A key component of paracrine secretion is usually extracellular vesicles (EVs), particularly the exosome portion that mainly contributes to the action of stem cells in which genetic information can be horizontally transferred between stem cells and tissue-injured cells. On the basis of the Anamorelin ability of microvesicles (MVs) to mimic stem cell properties, it is speculated that stem cell-derived MVs especially exosomes represent a relevant therapeutic option in regenerative medicine. In this review, we summarize the functions that MVs especially exosomes play in each type of stem cells. 2. Characteristics of Exosomes and Function Exosomes are one of the several groups of EVs which include ectosomes secreted directly from the plasma membranes and apoptotic body released from dying cells. Exosomes originate from the inward budding of the cell membranes followed by formation of multivesicular body (MVBs). When MVBs fuse with the plasma membranes, exosomes are released (Physique 1). Since they were discovered to be released from sheep reticulocytes, exosomes were once defined as unwanted proteins secreted from your cells and manifested as a membrane vesicle [8]. Currently, exosomes have been verified to be secreted from numerous cells including B cells [9], T cells [10], dendritic cells [11], platelets [12], the Schwann cells [13], tumor cells [14], cardiomyocytes [15], endothelial cells [16], and stem cells [17] among others. Moreover, exosomes are found in physiological fluids such as urine [18], plasma [19], and cerebral fluid [20] and even in organs such as thymus [21]. Exosomes are characterized by their diameters ranging from 30 to 120?nm and with a density in sucrose of 1 1.13C1.19?g/mL. Their membranes contain abundant cholesterol, sphingomyelin, ceramide, and lipid rafts. Besides, exosomes are enriched with numerous nucleic acids including mRNAs, microRNAs (miRNAs), and other noncoding RNAs [22]. These RNAs can be taken up by neighboring cells or remote cells, subsequently modulating recipient cells; on the other hand, RNAs are guarded from degradation after being packed into the exosomes or microvesicles, which altogether results in increased attention to exosomes and the carried RNAs. On this basis, an increasing quantity of mRNAs and miRNAs have been discovered in different cell-derived exosomes. Most exosomes have conserved a set of proteins such as heat shock proteins, HSP70 [23] and HSP90 [24], certain members of the tetraspanin superfamily of proteins, especially CD9, CD63, CD81, and CD82 [25], multivesicle related proteins such as Alix and TSG-101, and membrane transportation and merging proteins such as Rab GTPase and flotillin. In addition, exosomes contain unique tissue proteins that may reflect their cellular Anamorelin source. Mathivanan and Simpson [26] set up the ExoCarta, a freely accessible Anamorelin database listing proteins and RNAs that have been found in exosomes. The representative characteristics of exosomes isolated from MSCs by transmission electron microscopy (TEM) and nanoparticle tracking analysis (NTA) are shown in Physique 2 [27]. When referring to the function of exosomes (Table 1), though not clarified yet, most of.