Mesenchymal stem cells (MSCs) are clinically useful due to their capacity for self-renewal, their immunomodulatory properties and tissue regenerative potential. These cells can be isolated from various tissues and exhibit different potential for clinical applications according to their origin, and thus comparative studies on MSCs from different tissues are essential. In this study, we investigated the immunophenotype, proliferative potential, multilineage differentiation and immunomodulatory capacity of MSCs derived from different tissue sources, namely bone marrow, adipose tissue, the placenta and umbilical cord blood. The gene expression profiles of stemness-related genes [octamer-binding transcription factor 4 (OCT4), sex determining region Y-box (SOX)2, MYC, Krüppel-like factor 4 (KLF4), NANOG, LIN28 and REX1] and lineage‑related and differentiation stage-related genes [B4GALNT1 (GM2/GS2 synthase), inhibin, beta A (INHBA), distal-less homeobox 5 (DLX5), runt-related transcription factor 2 (RUNX2), proliferator‑activated receptor gamma (PPARG), CCAAT/enhancer-binding protein alpha (C/EBPA), bone morphogenetic protein 7 (BMP7) and SOX9] were compared using RT-PCR. No significant differences in growth rate, colony-forming efficiency and immunophenotype were observed. Our results demonstrated that MSCs derived from bone marrow and adipose tissue shared not only in vitro tri-lineage differentiation potential, but also gene expression profiles. While there was considerable inter-donor variation in DLX5 expression between MSCs derived from different tissues, its expression appears to be associated with the osteogenic potential of MSCs. Bone marrow-derived MSCs (BM-MSCs) significantly inhibited allogeneic T cell proliferation possibly via the high levels of the immunosuppressive cytokines, IL10 and TGFB1. Although MSCs derived from different tissues and fibroblasts share many characteristics, some of the marker genes, such as B4GALNT1 and DLX5 may be useful for the characterization of MSCs derived from different tissue sources. Collectively, our results suggest that, based on their tri-lineage differentiation potential and immunomodulatory effects, BM-MSCs and adipose tissue-derived MSCs (A-MSCs) represent the optimal stem cell source for tissue engineering and regenerative medicine.

Transplantation of mesenchymal stem cells (MSCs) was reported to improve functional outcomes in a rat model of ischemic stroke, and subsequent studies suggest that MSC-derived microvesicles (MVs) can replace the beneficial effects of MSCs. Here, we evaluated three different MSC-derived MVs, including MVs from untreated MSCs (MSC-MVs), MVs from MSCs treated with normal rat brain extract (NBE-MSC-MVs), and MVs from MSCs treated with stroke-injured rat brain extract (SBE-MSC-MVs), and tested their effects on ischemic brain injury induced by permanent middle cerebral artery occlusion (pMCAO) in rats. NBE-MSC-MVs and SBE-MSC-MVs had significantly greater efficacy than MSC-MVs for ameliorating ischemic brain injury with improved functional recovery. We found similar profiles of key signalling proteins in NBE-MSC-MVs and SBE-MSC-MVs, which account for their similar therapeutic efficacies. Immunohistochemical analyses suggest that brain-extract—treated MSC-MVs reduce inflammation, enhance angiogenesis, and increase endogenous neurogenesis in the rat brain. We performed mass spectrometry proteomic analyses and found that the total proteomes of brain-extract—treated MSC-MVs are highly enriched for known vesicular proteins. Notably, MSC-MV proteins upregulated by brain extracts tend to be modular for tissue repair pathways. We suggest that MSC-MV proteins stimulated by the brain microenvironment are paracrine effectors that enhance MSC therapy for stroke injury.

Mesenchymal stem cells (MSCs) are highly valued in regenerative medicine due to their ability to self-renew and differentiate into various cell types. Their therapeutic benefits are primarily due to their paracrine effects, in particular through extracellular vesicles (EVs), which are related to intercellular communication. Recent advances in EV production and extraction technologies highlight the potential of MSC-derived EVs (MSC-EVs) in tissue engineering and regenerative medicine. MSC-EVs offer several advantages over traditional cell therapies, including reduced toxicity and immunogenicity compared with whole MSCs. EVs carrying functional molecules such as growth factors, cytokines, and miRNAs play beneficial roles in tissue repair, fibrosis treatment, and scar prevention by promoting angiogenesis, skin cell migration, proliferation, extracellular matrix remodeling, and reducing inflammation. Despite the potential of MSC-EVs, there are several limitations to their use, including variability in quality, the need for standardized methods, low yield, and concerns about the composition of EVs and the potential risks. Overall, MSC-EVs are a promising alternative to cell-based therapies, and ongoing studies aim to understand their actions and optimize their use for better clinical outcomes in wound healing and skin regeneration.

Extracellular vesicles (EVs) are secreted membrane-enclosed nano-sized particles (40–1,000 nm) that deliver biological information between cells. The molecular composition of these subcellular particles includes growth factor receptors, ligands adhesion proteins, mRNA, miRNAs, lncRNA and lipids that are derived from donor cells. A number of studies demonstrated that stem cell-derived EVs are the key mediator of tissue repair and regeneration in multiple animal disease models. In addition, the composition of these particles is known to be altered in cancer and disease pathology suggesting them for useful in diagnostic and therapeutic purposes. Their endogenous origin and biological properties offer benefits over conventional drug delivery systems (DDS), such as liposome, synthetic nanoparticles and prompted the further application of EVs as drug delivery vehicles for chemical drugs, genetic materials and proteins. The contents of EVs can be efficiently modified by chemical, biological or physical means. Thus, EVs can be an innovative DDS as it can overcome physical and biological barriers and safely deliver therapeutic drugs to target tissues. In this minireview, we summarized current progress on the strategies of drug loading onto EVs; ex vivo and in vivo loading.