Autophagy Regulates the Effects of Adipose-derived Stem Cells Exosomes on Lipopolysaccharide-induced Pulmonary Microvascular Barrier Damage

Abstract Background: Exosomes have been recognized as being more effective than direct stem cell differentiation into functional target cells for protecting against tissue injury and promoting tissue repair. Our previous study demonstrated the protective effect of adipose-derived stem cells (ADSCs) on lipopolysaccharide (LPS)-induced acute lung injury and the effect of autophagy on ADSC functions, but the role of ADSC-derived exosomes (ADSC-Exos) and autophagy-mediated regulation of ADSC-Exos in LPS-induced pulmonary microvascular barrier damage remain unclear. Methods: LPS-induced pulmonary microvascular barrier injury was detected after ADSC-Exos pretreatment. Effects of autophagy on the function and bioactive miRNAs components of ADSC-Exos were assessed after inhibiting the cells autophagy in advance. Results: ADSC-Exo culture resulted in significant alleviation of LPS-induced microvascular barrier injury. The inhibition of autophagy markedly weakened the therapeutic effect of ADSC-Exos. In addition, autophagy inhibition changed the expression levels of the five specific miRNAs in exosomes; interleukin-1β（IL-1β）preconditioning promoted the expression of miR(miRNA)-21a but lowered the expressions of let-7-a-1, miR-143 and miR-145a, and did not affect the expression of miR-451a. Autophagy inhibition, however, has prohibited the expressions of all these miRNAs under IL-1β preconditioning. Conclusion: Our results indicate that ADSC-Exos protect against LPS-induced pulmonary microvascular barrier damage. Autophagy is a positive mediator of exosome function at least partly through controlling the expression of bioactive miRNAs in exosomes.

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Autophagy Regulates the Effects of Adipose-Derived Stem Cell Small Extracellular Vesicles On Lipopolysaccharide-Induced Pulmonary Microvascular Barrier Damage

10.21203/rs.3.rs-426888/v2 ◽

2022 ◽

Author(s):

Chichi Li ◽

Min Wang ◽

Wangjia Wang ◽

Yuping Li ◽

Dan Zhang

Keyword(s):

Stem Cell ◽

Acute Lung Injury ◽

Lung Injury ◽

Extracellular Vesicles ◽

Tissue Injury ◽

Stem Cell Differentiation ◽

Microvascular Endothelial Cell ◽

Target Cells ◽

Autophagy Inhibition

Abstract Background: Small extracellular vesicles (sEVs) have been recognized to be more effective than direct stem cell differentiation into functional target cells in preventing tissue injury and promoting tissue repair. Our previous study demonstrated the protective effect of adipose-derived stem cells (ADSCs) on lipopolysaccharide (LPS)-induced acute lung injury and the effect of autophagy on ADSC functions, but the role of ADSC-derived sEVs (ADSC-sEVs) and autophagy-mediated regulation of ADSC-sEVs in LPS-induced pulmonary microvascular barrier damage remains unclear. Methods: After treatment with sEVs from ADSCs with or without autophagy inhibition, LPS-induced human pulmonary microvascular endothelial cell (HPMVECs) barrier damage was detected. LPS-induced acute lung injury in mice was assessed in vivo after intravenous administration of sEVs from ADSCs with or without autophagy inhibition. The effects of autophagy on the bioactive miRNA components of ADSC-sEVs were assessed after prior inhibition of cell autophagy. Results: We found that ADSC-sEV effectively alleviated LPS-induced apoptosis, tight junction damage and high permeability of PMVECs. Moreover, in vivo administration of ADSC-sEV markedly inhibited LPS-triggered lung injury. However, autophagy inhibition, markedly weakened the therapeutic effect of ADSC-sEVs on LPS-induced PMVECs barrier damage and acute lung injury. In addition, autophagy inhibition, prohibited the expression of five specific miRNAs in ADSC-sEVs -under LPS-induced inflammatory conditions. Conclusions: Our results indicate that ADSC-sEVs protect against LPS-induced pulmonary microvascular barrier damage and acute lung injury. Autophagy is a positive mediator of sEVs function, at least in part through controlling the expression of bioactive miRNAs in sEVs.

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Rapid Magneto-Sonoporation of Adipose-Derived Cells

Materials ◽

10.3390/ma14174877 ◽

2021 ◽

Vol 14 (17) ◽

pp. 4877

Author(s):

Miriam Filippi ◽

Boris Dasen ◽

Arnaud Scherberich

Keyword(s):

Stem Cells ◽

Tissue Repair ◽

Morphological Changes ◽

Adipose Derived Stem Cells ◽

Resonance Imaging ◽

Membrane Resealing ◽

First Time ◽

Stimulation Of

By permeabilizing the cell membrane with ultrasound and facilitating the uptake of iron oxide nanoparticles, the magneto-sonoporation (MSP) technique can be used to instantaneously label transplantable cells (like stem cells) to be visualized via magnetic resonance imaging in vivo. However, the effects of MSP on cells are still largely unexplored. Here, we applied MSP to the widely applicable adipose-derived stem cells (ASCs) for the first time and investigated its effects on the biology of those cells. Upon optimization, MSP allowed us to achieve a consistent nanoparticle uptake (in the range of 10 pg/cell) and a complete membrane resealing in few minutes. Surprisingly, this treatment altered the metabolic activity of cells and induced their differentiation towards an osteoblastic profile, as demonstrated by an increased expression of osteogenic genes and morphological changes. Histological evidence of osteogenic tissue development was collected also in 3D hydrogel constructs. These results point to a novel role of MSP in remote biophysical stimulation of cells with focus application in bone tissue repair.

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Autophagy regulates the therapeutic potential of adipose-derived stem cells in LPS-induced pulmonary microvascular barrier damage

Cell Death and Disease ◽

10.1038/s41419-019-2037-8 ◽

2019 ◽

Vol 10 (11) ◽

Cited By ~ 3

Author(s):

Chichi Li ◽

Jingye Pan ◽

Lechi Ye ◽

Honglei Xu ◽

Beibei Wang ◽

...

Keyword(s):

Stem Cells ◽

Lung Injury ◽

Therapeutic Potential ◽

Microvascular Endothelial Cell ◽

Adipose Derived Stem Cells ◽

Protective Effects ◽

Paracrine Effects ◽

Autophagy Inhibition ◽

Lps Treatment

Abstract Adipose-derived stem cells (ADSCs) have been shown to be beneficial in some pulmonary diseases, and the paracrine effect is the major mechanism underlying ADSC-based therapy. Autophagy plays a crucial role in maintaining stem cell homeostasis and survival. However, the role of autophagy in mediating ADSC paracrine effects has not been thoroughly elucidated. We examined whether ADSCs participate in lipopolysaccharide (LPS)-induced pulmonary microvascular endothelial cell (PMVEC) barrier damage in a paracrine manner and illuminated the role of autophagy in regulating ADSC paracrine effects. PMVECs and ADSCs with or without autophagy inhibition were cocultured without intercellular contact, and the microvascular barrier function was assessed after LPS treatment. ADSC paracrine function was evaluated by detecting essential growth factors for endothelial cells. For in vivo experiments, ADSCs with or without autophagy inhibition were transplanted into LPS-induced lung-injury mice, and lung injury was assessed. ADSCs significantly alleviated LPS-induced microvascular barrier injury. In addition, ADSC paracrine levels of VEGF, FGF, and EGF were induced by LPS treatment, especially in the coculture condition. Inhibiting autophagy weakened the paracrine function and the protective effects of ADSCs on microvascular barrier injury. Moreover, ADSC transplantation alleviated LPS-induced lung injury, and inhibiting autophagy markedly weakened the therapeutic effect of ADSCs on lung injury. Together, these findings show that ADSC paracrine effects play a vital protective role in LPS-induced pulmonary microvascular barrier injury. Autophagy is a positive mediating factor in the paracrine process. These results are helpful for illuminating the role and mechanism of ADSC paracrine effects and developing effective therapies in acute lung injury.

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Proteomic Analysis of Exosomes from Adipose-Derived Mesenchymal Stem Cells: A Novel Therapeutic Strategy for Tissue Injury

BioMed Research International ◽

10.1155/2020/6094562 ◽

2020 ◽

Vol 2020 ◽

pp. 1-10 ◽

Cited By ~ 4

Author(s):

Xin Xing ◽

Shuang Han ◽

Gu Cheng ◽

Yifeng Ni ◽

Zhi Li ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Proteomic Analysis ◽

Tissue Repair ◽

Tissue Injury ◽

Protein Profile ◽

Cell Communication ◽

Average Diameter ◽

Target Cells ◽

General Function

Exosomes are extracellular membranous nanovesicles that mediate local and systemic cell-to-cell communication by transporting functional molecules, such as proteins, into target cells, thereby affecting the behavior of receptor cells. Exosomes originating from adipose-derived mesenchymal stem cells (ADSCs) are considered a multipotent and abundant therapeutic tool for tissue injury. To investigate ADSC-secreted exosomes and their potential function in tissue repair, we isolated exosomes from the supernatants of ADSCs via ultracentrifugation, characterized them via transmission electron microscopy, nanoparticle tracking analysis, and Western blot analysis. Then, we determined their protein profile via proteomic analysis. Results showed that extracellular vesicles, which have an average diameter of 116 nm, exhibit a cup-shaped morphology and express exosomal markers. A total of 1,185 protein groups were identified in the exosomes. Gene Ontology analysis indicated that exosomal proteins are mostly derived from cells mainly involved in protein binding. Protein annotation via the Cluster of Orthologous Groups system indicated that most proteins were involved in general function prediction, posttranslational modification, protein turnover, and chaperoning. Further, pathway analysis revealed that most of the proteins obtained participated in metabolic pathways, focal adhesion, regulation of the actin cytoskeleton, and microbial metabolism. Some tissue repair-related signaling pathways were also discovered. The identified molecules might serve as potential therapeutic targets for future studies.

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Stamina-Enhancing Effects of Human Adipose-Derived Stem Cells

Cell Transplantation ◽

10.1177/09636897211035409 ◽

2021 ◽

Vol 30 ◽

pp. 096368972110354

Author(s):

Eun-Jung Yoon ◽

Hye Rim Seong ◽

Jangbeen Kyung ◽

Dajeong Kim ◽

Sangryong Park ◽

...

Keyword(s):

Physical Activity ◽

Stem Cells ◽

Locomotor Activity ◽

Tissue Injury ◽

Male Rats ◽

Adipose Derived Stem Cells ◽

Sprague Dawley ◽

Serum Triglycerides

Stamina-enhancing effects of human adipose derived stem cells (hADSCs) were investigated in young Sprague-Dawley rats. Ten-day-old male rats were transplanted intravenously (IV) or intracerebroventricularly (ICV) with hADSCs (1 × 106 cells/rat), and physical activity was measured by locomotor activity and rota-rod performance at post-natal day (PND) 14, 20, 30, and 40, as well as a forced swimming test at PND 41. hADSCs injection increased the moving time in locomotor activity, the latency in rota-rod performance, and the maximum swimming time. For the improvement of physical activity, ICV transplantation was superior to IV injection. In biochemical analyses, ICV transplantation of hADSCs markedly reduced serum creatine phosphokinase, lactate dehydrogenase, alanine transaminase, and muscular lipid peroxidation, the markers for muscular and hepatic injuries, despite the reduction in muscular glycogen and serum triglycerides as energy sources. Notably, hADSCs secreted brain-derived neurotrophic factor (BDNF) and nerve growth factor in vitro, and increased the level of BDNF in the brain and muscles in vivo. The results indicate that hADSCs enhance physical activity including stamina not only by attenuating tissue injury, but also by strengthening the muscles via production of BDNF.

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Modulation of Differentiation of Embryonic Stem Cells by Polypyrrole: The Impact on Neurogenesis

International Journal of Molecular Sciences ◽

10.3390/ijms22020501 ◽

2021 ◽

Vol 22 (2) ◽

pp. 501

Author(s):

Kateřina Skopalová ◽

Katarzyna Anna Radaszkiewicz ◽

Věra Kašpárková ◽

Jaroslav Stejskal ◽

Patrycja Bober ◽

...

Keyword(s):

Stem Cells ◽

Embryonic Stem Cells ◽

Embryonic Stem ◽

Stem Cell Differentiation ◽

Active Role ◽

Low Molecular Weight ◽

Conducting Materials ◽

The Impact ◽

Erk Kinase

The active role of biomaterials in the regeneration of tissues and their ability to modulate the behavior of stem cells in terms of their differentiation is highly advantageous. Here, polypyrrole, as a representantive of electro-conducting materials, is found to modulate the behavior of embryonic stem cells. Concretely, the aqueous extracts of polypyrrole induce neurogenesis within embryonic bodies formed from embryonic stem cells. This finding ledto an effort to determine the physiological cascade which is responsible for this effect. The polypyrrole modulates signaling pathways of Akt and ERK kinase through their phosphorylation. These effects are related to the presence of low-molecular-weight compounds present in aqueous polypyrrole extracts, determined by mass spectroscopy. The results show that consequences related to the modulation of stem cell differentiation must also be taken into account when polypyrrole is considered as a biomaterial.

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