- Thermoresponsive Gel Embedding Adipose Stem Cell-Derived Extracellular Vesicles Promotes Esophageal Fistula Healing in a Thermo-Actuated Delivery Strategy. [Journal Article]
- ANACS Nano 2018 Sep 19
- Extracellular vesicles (EVs) are increasingly envisioned to be the next-generation of biological proregenerative nanotherapeutic agents, as already demonstrated for heart, kidney, liver, lung injury,...
Extracellular vesicles (EVs) are increasingly envisioned to be the next-generation of biological proregenerative nanotherapeutic agents, as already demonstrated for heart, kidney, liver, lung injury, brain and skin regeneration. Herein, we explore another potential EV therapeutic application, for fistula healing, together with a local minimally-invasive delivery strategy. Allogenic extracellular vesicles (EVs) from adipose tissue-derived stromal cells (ADSCs) are administered in a porcine fistula model through a thermoresponsive pluronic F-127 (PF-127) gel, injected locally at 4°C and gelling at body temperature to retain EVs in the entire fistula tract. Complete fistula healing is reported to be 100% for the gel + EVs group, 67% for the gel group and 0% for the control, supporting a therapeutic use of Pluronic F-127 gel alone or combined with EVs. However, only the combination of gel and EVs results in a statistically significant (i) reduction of fibrosis, (ii) decline of inflammatory response, (iii) decrease in the density of myofibroblasts and (iv) increase of angiogenesis. Overall, we demonstrate that ADSC-EV delivery into a PF-127 gel represents a successful local minimally-invasive strategy to induce a therapeutic effect in a swine fistula model. Our study brings prospects in EV administration strategies and in the management of postoperative fistulas.
- Therapeutic potential of extracellular vesicles derived from human mesenchymal stem cells in a model of progressive multiple sclerosis. [Journal Article]
- PlosPLoS One 2018; 13(9):e0202590
- Extracellular vesicles (EVs) have emerged as important mediators of intercellular communication and as possible therapeutic agents in inflammation-mediated demyelinating diseases, including multiple ...
Extracellular vesicles (EVs) have emerged as important mediators of intercellular communication and as possible therapeutic agents in inflammation-mediated demyelinating diseases, including multiple sclerosis (MS). In the present study, we investigated whether intravenously administered EVs derived from mesenchymal stem cells (MSCs) from human adipose tissue might mediate recovery in Theiler's murine encephalomyelitis virus (TMEV)-induced demyelinating disease, a progressive model of MS. SJL/J mice were subjected to EV treatment once the disease was established. We found that intravenous EV administration improved motor deficits, reduced brain atrophy, increased cell proliferation in the subventricular zone and decreased inflammatory infiltrates in the spinal cord in mice infected with TMEV. EV treatment was also capable of modulating neuroinflammation, given glial fibrillary acidic protein and Iba-1 staining were reduced in the brain, whereas myelin protein expression was increased. Changes in the morphology of microglial cells in the spinal cord suggest that EVs also modulate the activation state of microglia. The clear reduction in plasma cytokine levels, mainly in the Th1 and Th17 phenotypes, in TMEV mice treated with EVs confirms the immunomodulatory ability of intravenous EVs. According to our results, EV administration attenuates motor deficits through immunomodulatory actions, diminishing brain atrophy and promoting remyelination. Further studies are necessary to establish EV delivery as a possible therapy for the neurodegenerative phase of MS.
- Intercellular Communication between Airway Epithelial Cells is Mediated by Exosome-Like Vesicles. [Journal Article]
- AJAm J Respir Cell Mol Biol 2018 Sep 19
- Airway epithelium structure/function can be altered by local inflammatory/immune signals, and this process is called epithelial remodeling. The mechanism by which this innate response is regulated, w...
Airway epithelium structure/function can be altered by local inflammatory/immune signals, and this process is called epithelial remodeling. The mechanism by which this innate response is regulated, which causes mucin/mucus overproduction, is largely unknown. Exosomes are nano-vesicles that can be secreted and internalized by cells to transport cellular cargo, such as proteins, lipids, and miRNA. The objective of this study was to understand the role exosomes play in airway remodeling through cell-cell communication. We utilized two different human airway cell cultures: primary tracheobronchial (HTBE) cells and a cultured airway epithelial cell line (Calu-3). After intercellular exosomal transfer, comprehensive proteomic and genomic characterization of cell secretions and exosomes was performed. Quantitative proteomics and exosomal miRNA analysis profiles indicated that the two cell types are fundamentally distinct. HTBE cell secretions were typically dominated by fundamental innate/protective proteins, including mucin MUC5B, and Calu-3 cell secretions were dominated by pathology-associated proteins, including mucin MUC5AC. After exosomal transfer/intake, approximately 20% of proteins, including MUC5AC and MUC5B, were significantly altered in HTBE secretions. After exosome transfer, approximately 90 miRNAs (~4%) were upregulated in HTBE exosomes, whereas Calu-3 exosomes exhibited a preserved miRNA profile. Together, our data suggest that the transfer of exosomal cargo between airway epithelial cells significantly alters the qualitative and quantitative profiles of airway secretions, including mucin hypersecretion, and the miRNA cargo of exosomes in target cells. This finding indicates that cellular information can be carried between airway epithelial cells via exosomes, which may play an important role in airway biology and epithelial remodeling.
- Relationship of Seminal Megavesicles, Prostate Median Cysts, and Genotype in Autosomal Dominant Polycystic Kidney Disease. [Journal Article]
- JMJ Magn Reson Imaging 2018 Sep 19
- CONCLUSIONS: ADPKD is associated with prostate median cysts near ejaculatory ducts. These cysts correlate with seminal megavesicles (dilated to >10 mm) which predict a 10-fold greater likelihood of PKD1 vs. PKD2 mutation. Cysts elsewhere in the prostate are not related to ADPKD.
- Egg Yolk Extracts as Potential Liposomes Shell Material: Composition Compared with Vesicles Characteristics. [Journal Article]
- JFJ Food Sci 2018 Sep 19
- Our aim was to propose simple extraction process to obtain phospholipids along with yolk-derived vitamins and fats. Five extracts marked as ethanol/acetone, methanol-chloroform/acetone, hot ethanol, ...
Our aim was to propose simple extraction process to obtain phospholipids along with yolk-derived vitamins and fats. Five extracts marked as ethanol/acetone, methanol-chloroform/acetone, hot ethanol, hexane, and cold ethanol were developed and compared. Extracts' compositions were analyzed in terms of phospholipid, polar and nonpolar fraction, cholesterol, carotenoids, and tocopherols content. Further, liposomes prepared from extracts were characterized. The highest extraction efficiency was achieved by a one-step hexane procedure. However, that sample, in contrast to the other four extracts, revealed distinctively lower permeability when used for liposomes membrane formation. Principal component analysis proved that major components contents were decisive for liposomes membranes permeability, whereas minor constituents' content controlled zeta potential and Z-average size.
- Exosomes in HNSCC plasma as surrogate markers of tumour progression and immune competence. [Journal Article]
- CEClin Exp Immunol 2018 Sep 19
- Exosomes in plasma of head and neck squamous cell carcinoma (HNSCC) patients comprise subsets of vesicles derived from various cells. Recently, we separated CD3(+) from CD3(-) exosomes by immune capt...
Exosomes in plasma of head and neck squamous cell carcinoma (HNSCC) patients comprise subsets of vesicles derived from various cells. Recently, we separated CD3(+) from CD3(-) exosomes by immune capture. CD3(-) exosomes were largely tumour-derived (CD44v3+ ). Both subsets carried immunosuppressive proteins and inhibited functions of human immune cells. The role of these subsets in immune cell reprogramming by the tumour was investigated by focusing on the adenosine pathway components. Spontaneous adenosine production by CD3(+) or CD3(-) exosomes was measured by mass spectrometry, as was the production of adenosine by CD4+ CD39+ regulatory T cells (Treg ) co-incubated with these exosomes. The highest level of CD39/CD73 ectoenzymes and of adenosine production was found in CD3(-) exosomes in patients with the stages III/IV HNSCCs). Also, the production of 5'-AMP and purines was significantly higher in Treg co-incubated with CD3(-) than CD3(+) exosomes. Consistently, CD26 and adenosine deaminase (ADA) levels were higher in CD3(+) than CD3(-) exosomes. ADA and CD26 levels in CD3(+) exosomes were significantly higher in patients with early (stages I/II) than advanced (stages III/IV) disease. HNSCC patients receiving and responding to photodynamic therapy had increased ADA levels in CD3(+) exosomes with no increase in CD3(-) exosomes. The opposite roles of CD3(+) ADA+ CD26+ and CD3(-) CD44v3+ adenosine-producing exosomes in early versus advanced HNSCC suggest that, like their parent cells, these exosomes serve as surrogates of immune suppression in cancer.
- Self-assembly of a redox-active bolaamphiphile into supramolecular vesicles. [Journal Article]
- OBOrg Biomol Chem 2018 Sep 19
- The synthesis and self-assembly of a water-soluble bolaamphiphilic cyclopenta[hi]aceanthrylene derivative is described. Self-assembly in aqueous medium leads to the formation of supramolecular vesicl...
The synthesis and self-assembly of a water-soluble bolaamphiphilic cyclopenta[hi]aceanthrylene derivative is described. Self-assembly in aqueous medium leads to the formation of supramolecular vesicles with intense absorption bands over an extended range of the UV/vis spectral region and a narrow HOMO-LUMO bandgap of 1.65 eV.
- Changes in the biochemical taste of cytoplasmic and cell-free DNA are major fuels for inflamm-aging. [Review]
- SISemin Immunol 2018 Sep 15
- Inflamm-aging depicts the progressive activation of the innate immune system that accompanies human aging. Its role as a disease-predisposing condition has been proposed, but its molecular basis is s...
Inflamm-aging depicts the progressive activation of the innate immune system that accompanies human aging. Its role as a disease-predisposing condition has been proposed, but its molecular basis is still poorly understood. A wealth of literature conveys that, particularly upon stress, nuclear and mitochondrial genomes are released into the cytoplasmic and extracellular compartments. Cytoplasmic (cy) and cell-free (cf) DNA pools trigger inflammation and innate immunity at local and systemic level. In particular, cyDNA plays a crucial role in the phenomenon of cell senescence and in the cognate pro-inflammatory secretome. Here we propose that changes in a variety of biochemical characteristics "tastes" of cy- and cf-DNA (e.g. the amount of 8-oxo-deoxy-guanosine and 5-methyl-deoxy-cytosine, the proportion of DNA hybridized with RNA) potentially affect the capability of these DNA pools to ignite the innate immune system. We also underpin that telomeric sequences are major components of the cy/cfDNA payload. Telomere shortening, a hallmark of aging, causes the depletion of telomeric sequences in cy/cfDNA pool, thus unleashing their potential to exert an age-related activation of the innate immune system. Finally, we posit that various sources of DNA (extracellular vesicles, the commensal metagenome and food) contribute to the cy/cfDNA payloads. We speculate that changes in the biochemical "taste" of cy/cfDNA are major modifiers of inflamm-aging.
- Breaking the barrier of cancer through liposome loaded with phytochemicals. [Journal Article]
- CDCurr Drug Deliv 2018 Sep 18
- Currently the most important cause of death is cancer. To treat the cancer there are a number of drugs existing in the market but no drug is found to be completely safe and effective. The toxicity of...
Currently the most important cause of death is cancer. To treat the cancer there are a number of drugs existing in the market but no drug is found to be completely safe and effective. The toxicity of the drugs is the key problem in the cancer chemotherapy. However, plants and plant derived bioactive molecule have proved safe and effective in the treatment of cancers. Phytochemicals that are found in fruits, vegetables, herbs, and plant extract have been usually used for treating cancer. It has been established that several herbal drug have a strong anticancer activity. However, their poor bioavailability, solubility, and stability have severely restricted their use. These problems can be overcome by incorporating the herbal drug in nanolipolomal vesicles. In last few decades researcher have used herbal drug loaded nanoliposome for the treatment and management of a variety of cancers. Presently, a number of liposomal formulations are on the market for the treatment of cancer and many more are in pipe line. This review discusses about the tumor microenvironment, targeting mechanism of bioactive phytochemicals to the tumor tissue, background of nanoliposome, and the potential therapeutic applications of different bioactive phytochemicals loaded nanoliposome in cancer therapy.
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- Extracellular vesicles derived from human umbilical cord mesenchymal stem cells alleviate rat hepatic ischemia-reperfusion injury by suppressing oxidative stress and neutrophil inflammatory response. [Journal Article]
- FJFASEB J 2018 Sep 18; :fj201800131RR
- Mesenchymal stem cells (MSCs) have been reported to exert therapeutic effects on immunoregulation, tissue repair, and regeneration from the bench to the bedside. Increasing evidence demonstrates that...
Mesenchymal stem cells (MSCs) have been reported to exert therapeutic effects on immunoregulation, tissue repair, and regeneration from the bench to the bedside. Increasing evidence demonstrates that extracellular vesicles (EVs) derived from MSCs could contribute to these effects and are considered as a potential replacement for stem cell-based therapies. However, the efficacy and underlying mechanisms of EV-based treatment in hepatic ischemia-reperfusion injury (IRI) remain unclear. Here, we demonstrated that human umbilical cord MSC-EVs (huc-MSC-EVs) could protect against IRI-induced hepatic apoptosis by reducing the infiltration of neutrophils and alleviating oxidative stress in hepatic tissue in vivo. Meanwhile, huc-MSC-EVs reduced the respiratory burst of neutrophils and prevented hepatocytes from oxidative stress-induced cell death in vitro. Interestingly, we found that the mitochondria-located antioxidant enzyme, manganese superoxide dismutase (MnSOD), was encapsulated in huc-MSC-EVs and reduced oxidative stress in the hepatic IRI model. Knockdown of MnSOD in huc-MSCs decreased the level of MnSOD in huc-MSC-EVs and attenuated the anti-apoptosis and antioxidant capacities of huc-MSC-EVs, which could be partially rescued by MnSOD mimetic manganese (III) 5,10,15,20-tetrakis (4-benzoic acid) porphyrin (MnTBAP). In summary, these findings provide new clues to reveal the therapeutic effects of huc-MSC-EVs on hepatic IRI and evaluate their preclinical application.-Yao, J., Zheng, J., Cai, J., Zeng, K., Zhou, C., Zhang, J., Li, S., Li, H., Chen, L., He, L., Chen, H., Fu, H., Zhang, Q., Chen, G., Yang, Y., Zhang, Y. Extracellular vesicles derived from human umbilical cord mesenchymal stem cells alleviate rat hepatic ischemia-reperfusion injury by suppressing oxidative stress and neutrophil inflammatory response.