Dataset Information

Adipose stem cell-derived nanovesicles inhibit emphysema primarily via an FGF2-dependent pathway.

ABSTRACT: Cell therapy using stem cells has produced therapeutic benefits in animal models of COPD. Secretory mediators are proposed as one mechanism for stem cell effects because very few stem cells engraft after injection into recipient animals. Recently, nanovesicles that overcome the disadvantages of natural exosomes have been generated artificially from cells. We generated artificial nanovesicles from adipose-derived stem cells (ASCs) using sequential penetration through polycarbonate membranes. ASC-derived artificial nanovesicles displayed a 100?nm-sized spherical shape similar to ASC-derived natural exosomes and expressed both exosomal and stem cell markers. The proliferation rate of lung epithelial cells was increased in cells treated with ASC-derived artificial nanovesicles compared with cells treated with ASC-derived natural exosomes. The lower dose of ASC-derived artificial nanovesicles had similar regenerative capacity compared with a higher dose of ASCs and ASC-derived natural exosomes. In addition, FGF2 levels in the lungs of mice treated with ASC-derived artificial nanovesicles were increased. The uptake of ASC-derived artificial nanovesicles was inhibited by heparin, which is a competitive inhibitor of heparan sulfate proteoglycan that is associated with FGF2 signaling. Taken together, the data indicate that lower doses of ASC-derived artificial nanovesicles may have beneficial effects similar to higher doses of ASCs or ASC-derived natural exosomes in an animal model with emphysema, suggesting that artificial nanovesicles may have economic advantages that warrant future clinical studies.

SUBMITTER: Kim YS

PROVIDER: S-EPMC5291836 | biostudies-other | 2017 Jan

REPOSITORIES: biostudies-other

ACCESS DATA

Publications

Adipose stem cell-derived nanovesicles inhibit emphysema primarily via an FGF2-dependent pathway.

Kim You-Sun YS Kim Ji-Young JY Cho RyeonJin R Shin Dong-Myung DM Lee Sei Won SW Oh Yeon-Mok YM

Experimental & molecular medicine 20170113 1

Cell therapy using stem cells has produced therapeutic benefits in animal models of COPD. Secretory mediators are proposed as one mechanism for stem cell effects because very few stem cells engraft after injection into recipient animals. Recently, nanovesicles that overcome the disadvantages of natural exosomes have been generated artificially from cells. We generated artificial nanovesicles from adipose-derived stem cells (ASCs) using sequential penetration through polycarbonate membranes. ASC- ...[more]

PMID: 28082743

Similar Datasets

Project description:BackgroundHeat shock protein B7 (HSPB7), which belongs to small heat shock protein family, has been reported to be involved in diverse biological processes and diseases. However, whether HSPB7 regulates osteogenic differentiation of human adipose derived stem cells (hASCs) remains unexplored.MethodsThe expression level of HSPB7 during the osteogenesis of hASCs was examined by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blot analysis. Lentivirus transfection was used to knock down or overexpress HSPB7, which enabled us to investigate the effect of HSPB7 on osteogenic differentiation of hASCs. U0126 and extracellular signal-regulated protein kinase 1/2 (ERK1/2) siRNA were used to identify the mechanism of the HSPB7/ERK1/2 axis in regulating osteogenic differentiation of hASCs. Moreover, ectopic bone formation in nude mice and osteoporosis mice model was used to investigate the effect of HSPB7 on osteogenesis in vivo.ResultsIn this study, we found the expression of HSPB7 was significantly downregulated during the osteogenic differentiation of hASCs. HSPB7 knockdown remarkably promoted osteogenic differentiation of hASCs, while HSPB7 overexpression suppressed osteogenic differentiation of hASCs both in vitro and in vivo. Moreover, we discovered that the enhancing effect of HSPB7 knockdown on osteogenic differentiation was related to the activation of extracellular signal-regulated protein kinase (ERK) signaling pathway. Inhibition of ERK signaling pathway with U0126 or silencing ERK1/2 effectively blocked the stimulation of osteogenic differentiation induced by HSPB7 knockdown. Additionally, we found that HSPB7 expression was markedly increased in mouse bone marrow mesenchymal stem cells (mBMSCs) from the osteoporotic mice which suggested that HSPB7 might be utilized as a potential target in the development of effective therapeutic strategies to treat osteoporosis and other bone diseases.ConclusionTaken together, these findings uncover a previously unrecognized function of HSPB7 in regulating osteogenic differentiation of hASCs, partly via the ERK signaling pathway.

Project description:Recent studies have shown that co-culture systems play an important role in bone tissue engineering. In this study, human dental pulp stem cells (hDPSCs) were co-cultured with human adipose-derived stem cells (hADSCs), and osteoblastic phenotypes were found to be enhanced in co-cultures compared with monocultures of hDPSCs or hADSCs. Furthermore, GW4869, an inhibitor of extracellular vesicle (EV) formation, suppressed the mineralization of co-cultured cells. Studies indicate that the therapeutic potential of DPSCs is realized through paracrine action, in which EVs play an important role. To study their role, we successfully obtained and identified hDPSC-derived extracellular vesicles (hDPSC-EVs), and further investigated their effects on hADSCs and the underlying mechanism. hADSCs were stimulated with hDPSC-EVs, which were found to promote the migration and mineralization of hADSCs. Moreover, hDPSC-EVs promoted osteogenic differentiation by enhancing the phosphorylation of ERK 1/2 and JNK in hADSCs. To investigate the specific proteins in EVs that might play a role in hADSC osteogenic differentiation, we performed proteomic analysis of hDPSC-EVs. We determined the top 30 enriched pathways, which notably included the insulin signaling pathway. The number of genes enriched in the insulin signaling pathway was the largest, in addition to the "protein processing in endoplasmic reticulum" term. The MAPK cascade is a typical downstream pathway mediating insulin signaling. To further study the effects of hDPSC-EVs on maxillofacial bone regeneration, we used hDPSC-EVs as a cell-free biomaterial in a model of mandibular defects in rats. To assess the therapeutic potential of EVs, we analyzed their proteome. Animal experiments demonstrated that hDPSC-EVs promoted the regeneration of bone defects. Overall, these results highlight the potential of hDPSC-EVs to induce lineage specific differentiation of hADSCs. The results also indicated the importance of considering hDPSC-EVs as biomimetic materials for clinical translation of treatments for oral maxillofacial defects.

Project description:Mesenchymal stem cells (MSCs) possess self-renewal and multipotential differentiation abilities, and they are thought to be one of the most reliable stem cell sources for a variety of cell therapies. Recently, cell therapy using MSCs has been studied as a novel therapeutic approach for cancers that show refractory progress and poor prognosis. MSCs from different tissues have different properties. However, the effect of different MSC properties on their application in anticancer therapies has not been thoroughly investigated. In this study, to characterize the anticancer therapeutic application of MSCs from different sources, we established two different kinds of human MSCs: umbilical cord blood-derived MSCs (UCB-MSCs) and adipose-tissue-derived MSCs (AT-MSCs). We used these MSCs in a coculture assay with primary glioblastoma multiforme (GBM) cells to analyze how MSCs from different sources can inhibit GBM growth. We found that UCB-MSCs inhibited GBM growth and caused apoptosis, but AT-MSCs promoted GBM growth. Terminal deoxynucleotidyl transferase-mediated biotinylated UTP nick-end labeling assay clearly demonstrated that UCB-MSCs promoted apoptosis of GBM via tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). TRAIL was expressed more highly by UCB-MSCs than by AT-MSCs. Higher mRNA expression levels of angiogenic factors (vascular endothelial growth factor, angiopoietin 1, platelet-derived growth factor, and insulin-like growth factor) and stromal-derived factor-1 (SDF-1/CXCL12) were observed in AT-MSCs, and highly vascularized tumors were developed when AT-MSCs and GBM were cotransplanted. Importantly, CXCL12 inhibited TRAIL activation of the apoptotic pathway in GBM, suggesting that AT-MSCs may support GBM development in vivo by at least two distinct mechanisms-promoting angiogenesis and inhibiting apoptosis. The opposite effects of AT-MSCs and UCB-MSCs on GBM clearly demonstrate that differences must be considered when choosing a stem cell source for safety in clinical application.

Dataset Information

Adipose stem cell-derived nanovesicles inhibit emphysema primarily via an FGF2-dependent pathway.

Publications

Adipose stem cell-derived nanovesicles inhibit emphysema primarily via an FGF2-dependent pathway.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets