Mesenchymal Stem Cell-Derived Exosomes: New Opportunity in Cell-Free Therapy

Sarvar, Davod Pashoutan; Shamsasenjan, Karim; Akbarzadehlaleh, Parvin

doi:10.15171/apb.2016.041

Cited by 122 publications

(98 citation statements)

References 88 publications

(39 reference statements)

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“…Instead, there is growing evidence MSCs may primarily act by a paracrine mechanism, namely by secreting exosomes/microvesicles. MSC-derived exosomes are smaller and less complex than their parental cells, and less immunogenic because of their lower content of membrane-bound proteins [96][97][98][99][100].…”

Section: The Therapeutic Potential Of Ivw-mscsmentioning

confidence: 99%

Direct conversion of human fibroblasts into therapeutically active vascular wall-typical mesenchymal stem cells

Steens

Unger

Klar

et al. 2019

Cell. Mol. Life Sci.

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Cell-based therapies using adult stem cells are promising options for the treatment of a number of diseases including autoimmune and cardiovascular disorders. Among these, vascular wall-derived mesenchymal stem cells (VW-MSCs) might be particularly well suited for the protection and curative treatment of vascular damage because of their tissue-specific action. Here we report a novel method for the direct conversion of human skin fibroblasts towards MSCs using a VW-MSC-specific gene code (HOXB7, HOXC6 and HOXC8) that directs cell fate conversion bypassing pluripotency. This direct programming approach using either a self-inactivating (SIN) lentiviral vector expressing the VW-MSC-specific HOX-code or a tetracyclinecontrolled Tet-On system for doxycycline-inducible gene expressions of HOXB7, HOXC6 and HOXC8 successfully mediated the generation of VW-typical MSCs with classical MSC characteristics in vitro and in vivo. The induced VW-MSCs (iVW-MSCs) fulfilled all criteria of MSCs as defined by the International Society for Cellular Therapy (ISCT). In terms of multipotency and clonogenicity, which are important specific properties to discriminate MSCs from fibroblasts, iVW-MSCs behaved like primary ex vivo isolated VW-MSCs and shared similar molecular and DNA methylation signatures. With respect to their therapeutic potential, these cells suppressed lymphocyte proliferation in vitro, and protected mice against vascular damage in a mouse model of radiation-induced pneumopathy in vivo, as well as ex vivo cultured human lung tissue. The feasibility to obtain patient-specific VW-MSCs from fibroblasts in large amounts by a direct conversion into induced VW-MSCs could potentially open avenues towards novel, MSC-based therapies.

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Section: The Therapeutic Potential Of Ivw-mscsmentioning

confidence: 99%

Direct conversion of human fibroblasts into therapeutically active vascular wall-typical mesenchymal stem cells

Steens

Unger

Klar

et al. 2019

Cell. Mol. Life Sci.

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“…To date, it has been reported that exosomes are released by several normal and cancer cells . Moreover, exosomes, isolated and characterized by different strategies (Table ).…”

Section: Introductionmentioning

confidence: 99%

Polyomavirus microRNAs circulating in biological fluids during viral persistence

Martelli

Giannecchini

2017

Reviews in Medical Virology

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Increasing evidence suggests that microRNA-mediated gene silencing, detected during exosome intercellular communication between cells, may be exploited by persistent human viruses. Recently, it has been reported that human polyomaviruses encode microRNAs that downregulate large T expression and target host factors, helping the virus to escape immune elimination. Consequently, viral microRNAs and their genetic variability may have roles in the induction of polyomavirus reactivation, the success of persistence or replication and the development of diseases. In vitro experiments have detected polyomavirus JC (JCPyV) microRNAs in exosomes obtained from cell supernatants after viral infection and showed that they can be carried into uninfected cells. JCPyV and BKPyV microRNAs have been sought in clinical samples obtained from patients with or at risk of severe polyomavirus-associated diseases and from healthy subjects. Variable expressions of JCPyV and BKPyV microRNAs circulating in blood, urine, and cerebrospinal fluid samples were found in patients who were polyomavirus DNA positive and were also observed in negative subjects. Differences in the relationship between the JCPyV and BKPyV microRNA expressions and viral DNA load have been observed. All the data point towards a potential role of polyomavirus exosome microRNAs in viral persistence and suggest that further work is warranted to define their role in viral reactivation and to identify potential new antiviral strategies targeting these viruses.

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“…A large body of evidence suggests that paracrine mechanisms mediated by soluble factors that are released from MSCs play an important role in improving disease progression (11–13). Upon receiving pathologic signals, like inflammatory signals, these bioactive factors are homed to the site of injury, where they inhibit proinflammatory responses, prevent apoptosis, and induce tissue-specific precursor cell differentiation (14).…”

mentioning

confidence: 99%

Anti‐inflammatory effects of hypoxia‐preconditioned human periodontal ligament cell secretome in an experimental model of multiple sclerosis: a key role of IL‐37

Giacoppo

Rajan

Diomede³

et al. 2017

The FASEB Journal

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Recent research has widely investigated the anti-inflammatory effects of mesenchymal stem cells and their secretory products, termed the secretome, in the treatment of multiple sclerosis (MS). The present study examined the capacity of the conditioned medium (CM) from human periodontal ligament stem cells (hPLSCs) under hypoxia (H-hPDLSCs-CM) to suppress experimental autoimmune encephalomyelitis (EAE), a murine model of MS. To induce EAE, female C57BL/6 mice were immunized with myelin oligodendroglial glycoprotein peptide35–55. At the onset of symptoms, H-hPDLSCs-CM was infused via the tail vein of mice. Our results demonstrate the efficacy of H-hPDLSCs-CM treatment in diminishing clinical and histologic disease score. A key finding from this study is the marked expression of anti-inflammatory cytokine IL-37, paralleled by the suppression of proinflammatory cytokines in mice with EAE that were treated with H-hPDLSCs-CM. In addition, a consequent modulation of oxidative stress, autophagic, and apoptotic markers was observed in mice with EAE after hPDLSCs-CM administration. In addition, to provide additional evidence of the molecular mechanisms that underlie H-hPDLSCs-CM, we investigated its therapeutic action in scratch injury–exposed NSC-34 neurons, an in vitro model of injury. This model reproduces severe inflammation and oxidative stress conditions as observed after EAE damage. In vitro results corroborate the ability of hPDLSCs-CM to modulate inflammatory, oxidative stress, and apoptotic pathways. Taken together, our findings suggest H-hPDLSCs-CM as a new pharmacologic opportunity for the management of MS.—Giacoppo, S., Thangavelu, S. R., Diomede, F., Bramanti, P., Conti, P., Trubiani, O., Mazzon, E. Anti-inflammatory effects of hypoxia-preconditioned human periodontal ligament cell secretome in an experimental model of multiple sclerosis: a key role of IL-37.

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Mesenchymal Stem Cell-Derived Exosomes: New Opportunity in Cell-Free Therapy

Cited by 122 publications

References 88 publications

Direct conversion of human fibroblasts into therapeutically active vascular wall-typical mesenchymal stem cells

Direct conversion of human fibroblasts into therapeutically active vascular wall-typical mesenchymal stem cells

Polyomavirus microRNAs circulating in biological fluids during viral persistence

Anti‐inflammatory effects of hypoxia‐preconditioned human periodontal ligament cell secretome in an experimental model of multiple sclerosis: a key role of IL‐37

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