The Role of Exosomes Derived From Mesenchymal Stromal Cells in Dermatology.
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ABSTRACT:
SUBMITTER: Quinones-Vico MI
PROVIDER: S-EPMC8058372 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:We have established early-gestation chorionic villus-derived placenta mesenchymal stromal cells (PMSCs) as a potential treatment for spina bifida (SB), a neural tube defect. Our preclinical studies demonstrated that PMSCs have the potential to cure hind limb paralysis in the fetal lamb model of SB via a paracrine mechanism. PMSCs exhibit neuroprotective function by increasing cell number and neurites, as shown by indirect coculture and direct addition of PMSC-conditioned medium to the staurosporine-induced apoptotic human neuroblastoma cell line, SH-SY5Y. PMSC-conditioned medium suppressed caspase activity in apoptotic SH-SY5Y cells, suggesting that PMSC secretome contributes to neuronal survival after injury. As a part of PMSC secretome, PMSC exosomes were isolated and extensively characterized; their addition to apoptotic SH-SY5Y cells mediated an increase in neurites, suggesting that they exhibit neuroprotective function. Proteomic and RNA sequencing analysis revealed that PMSC exosomes contain several proteins and RNAs involved in neuronal survival and development. Galectin 1 was highly expressed on the surface of PMSCs and PMSC exosomes. Preincubation of exosomes with anti-galectin 1 antibody decreased their neuroprotective effect, suggesting that PMSC exosomes likely impart their effect via binding of galectin 1 to cells. Future studies will include in-depth analyses of the role of PMSC exosomes on neuroprotection and their clinical applications.-Kumar, P., Becker, J. C., Gao, K., Carney, R. P., Lankford, L., Keller, B. A., Herout, K., Lam, K. S., Farmer, D. L., Wang, A. Neuroprotective effect of placenta-derived mesenchymal stromal cells: role of exosomes.
| S-EPMC6463921 | biostudies-literature
Project description:BackgroundMesenchymal stromal cells (MSCs) are a promising therapy for preventing chronic Graft-Versus-Host Disease (cGVHD) due to their potent immunomodulatory properties. However, the safety concerns regarding the use of MSCs remain unsolved, and conflicting effects are observed due to the heterogeneity of MSCs. Recently, exosomes were shown to mediate the paracrine effects of MSCs, making it a potential candidate for cell-free therapies. The aim of this study is to investigate the efficacy and safety of MSCs-derived exosomes (MSCs-exo) in an established cGVHD mouse model.MethodsBone marrow (BM)-derived MSCs were cultured, and the supernatants of these cultures were collected to prepare exosomes using ultracentrifugation. Exosomes from human dermal fibroblasts (Fib-exo) were used as a negative control. The cGVHD model was established, and tail vein injections of MSCs-exo or Fib-exo were administered once per week for 6 weeks. The symptoms and signs of cGVHD were monitored, and histopathological changes were detected by hematoxylin and eosin and Masson staining. The effects of MSCs-exo on Th17, Th1, and Treg were evaluated by flow cytometry, qPCR, and Luminex. In addition, human peripheral blood mononuclear cells (PBMCs) were stimulated and treated with MSCs-exo in vitro. IL-17-expressing Th17 and IL-10-expressing Treg were evaluated by flow cytometry, qPCR, and ELISA.ResultsWe found that MSCs-exo effectively prolonged the survival of cGVHD mice and diminished the clinical and pathological scores of cGVHD. Fibrosis in the skin, lung, and liver was significantly ameliorated by MSCs-exo application. In MSCs-exo treated mice, activation of CD4+ T cells and their infiltration into the lung were reduced. Of note, MSCs-exo exhibited potent immunomodulatory effects via the inhibition of IL-17-expressing pathogenic T cells and induction of IL-10-expressing regulatory cells during cGVHD. The expressions of Th17 cell-relevant transcription factors and pro-inflammatory cytokines was markedly reduced after MSCs-exo treatment. In vitro, MSCs-exo blocked Th17 differentiation and improved the Treg phenotype in PBMCs obtained from healthy donors and patients with active cGVHD, further indicating the regulatory effect of MSCs-exo on GVHD effector T cells.ConclusionsOur data suggested that MSCs-exo could improve the survival and ameliorate the pathologic damage of cGVHD by suppressing Th17 cells and inducing Treg. This finding provides a novel alternative approach for the treatment of cGVHD.
| S-EPMC6286548 | biostudies-literature
Project description:Exosomes are nanovesicles secreted by virtually all cells. Exosomes mediate the horizontal transfer of various macromolecules previously believed to be cell-autonomous in nature, including nonsecretory proteins, various classes of RNA, metabolites, and lipid membrane-associated factors. Exosomes derived from mesenchymal stem/stromal cells (MSCs) appear to be particularly beneficial for enhancing recovery in various models of disease. To date, there have been more than 200 preclinical studies of exosome-based therapies in a number of different animal models. Despite a growing number of studies reporting the therapeutic properties of MSC-derived exosomes, their underlying mechanism of action, pharmacokinetics, and scalable manufacturing remain largely outstanding questions. Here, we review the global trends associated with preclinical development of MSC-derived exosome-based therapies, including immunogenicity, source of exosomes, isolation methods, biodistribution, and disease categories tested to date. Although the in vivo data assessing the therapeutic properties of MSC-exosomes published to date are promising, several outstanding questions remain to be answered that warrant further preclinical investigation.
| S-EPMC7004029 | biostudies-literature
Project description:Mesenchymal stromal cells (MSCs) are a major component of the tumour microenvironment. A plethora of elegant studies focusing on tumour-derived MSCs have shown that they, unlike normal MSCs in other tissue, exhibit a strong ability to promote tumour progression. However, the mechanisms underlying the conversion of normal MSCs into tumour-associated MSCs are unknown. We report here a critical role of tumour cell-derived exosomes in endowing bone marrow-derived MSCs (BM-MSCs) with a tumour-favourable phenotype. Tumour cell-derived exosomes affected neither the growth factor production nor the immunosuppressive property of MSCs; rather, they endowed MSCs with a strong ability to promote macrophage infiltration into B16-F0 melanoma or EL-4 lymphoma. Ablation of macrophages by clodronate liposome administration reversed the tumour-promoting effect of MSCs educated by tumour cell-derived exosomes (TE-MSCs) on the tumour growth. By comparing the chemokine profile of BM-MSCs with that of TE-MSCs, we found that TE-MSCs produced a large amount of CCR2 ligands, CCL2 and CCL7, which are responsible for macrophage recruitment. CCR2-specific inhibitor was found to block the tumour-promoting effect of TE-MSCs. Thus, our investigations demonstrated that tumour cell-derived exosomes confer BM-MSCs the ability to enhance tumour growth. Therefore, we uncovered a novel mechanism underlying the conversion of normal MSCs to tumour-associated MSCs.
| S-EPMC5116561 | biostudies-literature
Project description:The oral cavity as the second most various microbial community in the body contains a broad spectrum of microorganisms which are known as the oral microbiome. The oral microbiome includes different types of microbes such as bacteria, fungi, viruses, and protozoa. Numerous factors can affect the equilibrium of the oral microbiome community which can eventually lead to orodental infectious diseases. Periodontitis, dental caries, oral leukoplakia, oral squamous cell carcinoma are some multifactorial infectious diseases in the oral cavity. In defending against infection, the immune system has an essential role. Depending on the speed and specificity of the reaction, immunity is divided into two different types which are named the innate and the adaptive responses but also there is much interaction between them. In these responses, different types of immune cells are present and recent evidence demonstrates that these cell types both within the innate and adaptive immune systems are capable of secreting some extracellular vesicles named exosomes which are involved in the response to infection. Exosomes are 30-150 nm lipid bilayer vesicles that consist of variant molecules, including proteins, lipids, and genetic materials and they have been associated with cell-to-cell communications. However, some kinds of exosomes can be effective on the pathogenicity of various microorganisms and promoting infections, and some other ones have antimicrobial and anti-infective functions in microbial diseases. These discrepancies in performance are due to the origin of the exosome. Exosomes can modulate the innate and specific immune responses of host cells by participating in antigen presentation for activation of immune cells and stimulating the release of inflammatory factors and the expression of immune molecules. Also, mesenchymal stromal/stem cells (MSCs)-derived exosomes participate in immunomodulation by different mechanisms. Ease of expansion and immunotherapeutic capabilities of MSCs, develop their applications in hundreds of clinical trials. Recently, it has been shown that cell-free therapies, like exosome therapies, by having more advantages than previous treatment methods are emerging as a promising strategy for the treatment of several diseases, in particular inflammatory conditions. In orodental infectious disease, exosomes can also play an important role by modulating immunoinflammatory responses. Therefore, MSCs-derived exosomes may have potential therapeutic effects to be a choice for controlling and treatment of orodental infectious diseases.
| S-EPMC8764367 | biostudies-literature
Project description:Due to their robust immunomodulatory capabilities, mesenchymal stem/stromal cells (MSCs) have been used as a cellular therapy for a number of human diseases. Part of the mechanism of action of MSCs is the production of extracellular vesicles (EVs) that contain proteins, nucleic acids, and lipids that transmit signals to recipient cells that change their biologic behavior. This review briefly summarizes the development of MSCs as a treatment for human diseases as well as describes our present understanding of exosomes; how they exert their effects on target cells, and how they are differentiated from other EVs. The current treatment paradigm for acute radiation syndrome (ARS) is discussed, and how MSCs and MSC derived exosomes are emerging as treatment options for treating patients after radiation exposure. Other conditions such as graft-versus-host disease and cardiovascular disease/stroke are discussed as examples to highlight the immunomodulatory and regenerative capacity of MSC-exosomes. Finally, a consideration is given to how these cell-based therapies could possibly be deployed in the event of a catastrophic radiation exposure event.
| S-EPMC7379234 | biostudies-literature
Project description:Mesenchymal stromal/stem cells (MSCs) are widely utilized in cell therapy because of their robust immunomodulatory and regenerative properties. Their paracrine activity is one of the most important features that contribute to their efficacy. Recently, it has been demonstrated that the production of various factors via extracellular vesicles, especially exosomes, governs the principal efficacy of MSCs after infusion in experimental models. Compared to MSCs themselves, MSC-derived exosomes (MSC-Exos) have provided significant advantages by efficiently decreasing unfavorable adverse effects, such as infusion-related toxicities. MSC-Exos is becoming a promising cell-free therapeutic tool and an increasing number of clinical studies started to assess the therapeutic effect of MSC-Exos in different diseases. In this review, we summarized the ongoing and completed clinical studies using MSC-Exos for immunomodulation, regenerative medicine, gene delivery, and beyond. Additionally, we summarized MSC-Exos production methods utilized in these studies with an emphasis on MSCs source, MSC-Exos isolation methods, characterization, dosage, and route of administration. Lastly, we discussed the current challenges and future directions of exosome utilization in different clinical studies as a novel therapeutic strategy.
| S-EPMC10079493 | biostudies-literature
Project description:BM mesenchymal stromal cells (BM-MSCs) support multiple myeloma (MM) cell growth, but little is known about the putative mechanisms by which the BM microenvironment plays an oncogenic role in this disease. Cell-cell communication is mediated by exosomes. In this study, we showed that MM BM-MSCs release exosomes that are transferred to MM cells, thereby resulting in modulation of tumor growth in vivo. Exosomal microRNA (miR) content differed between MM and normal BM-MSCs, with a lower content of the tumor suppressor miR-15a. In addition, MM BM-MSC-derived exosomes had higher levels of oncogenic proteins, cytokines, and adhesion molecules compared with exosomes from the cells of origin. Importantly, whereas MM BM-MSC-derived exosomes promoted MM tumor growth, normal BM-MSC exosomes inhibited the growth of MM cells. In summary, these in vitro and in vivo studies demonstrated that exosome transfer from BM-MSCs to clonal plasma cells represents a previously undescribed and unique mechanism that highlights the contribution of BM-MSCs to MM disease progression.
| S-EPMC3613927 | biostudies-literature
Project description:Inflammatory response mediated by immune cells is either directly or indirectly regulated by mesenchymal stromal cells (MSCs). Accumulating evidence suggests that thrombospondin-1 (TSP-1) is highly expressed in response to inflammation. In this work, we isolated and identified human thymic mesenchymal stromal cells (tMSCs) and detected the expression of TSP-1. We found that tMSCs expressed TSP-1 and Poly (I:C) or LPS treatment promoted the expression of TSP-1. Further, we isolated and identified exosomes originating from tMSCs (MEXs). Notably, exosomes derived from LPS-pretreated tMSCs (MEXsLPS) promoted the polarization of macrophages to M1-like phenotype and IL-6, TNF-α secretion as well as the pro-inflammatory differentiation of CD4+T cells into Th17 cells. Upon silencing the expression of TSP-1 in tMSCs, the pro-inflammatory effects of MEXsLPS were suppressed. Therefore, these findings uncovered TSP-1 as the principal factor in MEXsLPS pro-inflammatory regulation.
| S-EPMC8521535 | biostudies-literature
Project description:The human endometrial stromal cells (hEndoSCs) could maintain endometrial homeostasis and play a critical role in repairing endometrial injury. Mesenchymal stem cells (MSCs) significantly increase the proliferation of damaged hEndoSCs and protect them from apoptosis. Recent studies indicated that exosomes derived from stem cells could be recruited to damaged tissues for regeneration, which exhibit the potential for stem cell therapy as therapeutic vectors. In this study, we isolated human umbilical cord mesenchymal stem cell-derived exosomes (hUCMSC-Exos) and investigated the effects of hUCMSC-Exos on mifepristone-induced hEndoSC injury. Exosome uptake and cell proliferation as well as cell apoptosis of damaged hEndoSCs treated with hUCMSC-Exos were detected. We also assessed the expression of apoptosis-related proteins and the PTEN/AKT signaling pathway. We found hUCMSC-Exos improved the proliferation of damaged hEndoSCs and protected hEndoSCs from the mifepristone-induced apoptosis. hUCMSC-Exos upregulated Bcl-2 level as well as downregulated Cleaved Caspase-3 level and activated the PTEN/AKT signaling pathway to regulate the proliferation and antiapoptosis. These results indicated hUCMSC-Exos protected hEndoSCs from mifepristone-induced apoptosis and played an active role in repairing the damaged hEndoSCs through the PTEN/AKT signaling pathway in vitro. hUCMSC-Exos may hold great promise in the cell-free therapy of endometrial injury.
| S-EPMC7204211 | biostudies-literature