PDGF enhances the protective effect of adipose stem cell-derived extracellular vesicles in a model of acute hindlimb ischemia

Background. Although mesenchymal stem cell- (MSC-) derived extracellular vesicles (EVs) are as effective as MSCs in the suppression of allergic airway inflammation, few studies have explored the molecular mechanisms of MSC-derived EVs in allergic airway diseases. The objective of this study was to evaluate differentially expressed genes (DEGs) in the lung associated with the suppression of allergic airway inflammation using adipose stem cell- (ASC-) derived EVs. Methods. C57BL/6 mice were sensitized to ovalbumin (OVA) by intraperitoneal injection and challenged intranasally with OVA. To evaluate the effect of ASC-derived EVs on allergic airway inflammation, 10 μg/50 μL of EVs were administered intranasally prior to OVA challenge. Lung tissues were removed and DEGs were compared pairwise among the three groups. DEG profiles and hierarchical clustering of the identified genes were analyzed to evaluate changes in gene expression. Real-time PCR was performed to determine the expression levels of genes upregulated after treatment with ASC-derived EVs. Enrichment analysis based on the Gene Ontology (GO) database and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were also performed to further identify the function of DEGs. Results. Expression of paraoxonase 1 (PON1), brain-expressed X-linked 2 (Bex2), insulin-like growth factor binding protein 6 (Igfbp6), formyl peptide receptor 1 (Fpr1), and secretoglobin family 1C member 1 (Scgb1c1) was significantly increased in asthmatic mice following treatment with ASC-derived EVs. GO enrichment and KEGG pathway analysis showed that these genes were strongly associated with immune system processes and their regulation, cellular processes, single-organism processes, and biological regulation. Conclusion. These results suggest that the DEGs identified in this study (PON1, Bex2, Igfbp6, Fpr1, and Scgb1c1) may be involved in the amelioration of allergic airway inflammation by ASC-derived EVs.

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Adipose Stem Cell-Derived Extracellular Vesicles Induce Proliferation of Schwann Cells via Internalization

Cells ◽

10.3390/cells9010163 ◽

2020 ◽

Vol 9 (1) ◽

pp. 163 ◽

Cited By ~ 6

Author(s):

Maximilian Haertinger ◽

Tamara Weiss ◽

Anda Mann ◽

Annette Tabi ◽

Victoria Brandel ◽

...

Keyword(s):

Image Analysis ◽

Stem Cell ◽

Extracellular Vesicles ◽

Live Cell Imaging ◽

Cell Imaging ◽

Live Cell ◽

Automated Image Analysis ◽

Dependent Manner ◽

Adipose Stem Cell ◽

Silica Beads

Recent studies showed a beneficial effect of adipose stem cell-derived extracellular vesicles (ADSC-EVs) on sciatic nerve repair, presumably through Schwann cell (SC) modulation. However, it has not yet been elucidated whether ADSC-EVs exert this supportive effect on SCs by extracellular receptor binding, fusion to the SC membrane, or endocytosis mediated internalization. ADSCs, ADSC-EVs, and SCs were isolated from rats and characterized according to associated marker expression and properties. The proliferation rate of SCs in response to ADSC-EVs was determined using a multicolor immunofluorescence staining panel followed by automated image analysis. SCs treated with ADSC-EVs and silica beads were further investigated by 3-D high resolution confocal microscopy and live cell imaging. Our findings demonstrated that ADSC-EVs significantly enhanced the proliferation of SCs in a time- and dose-dependent manner. 3-D image analysis revealed a perinuclear location of ADSC-EVs and their accumulation in vesicular-like structures within the SC cytoplasm. Upon comparing intracellular localization patterns of silica beads and ADSC-EVs in SCs, we found striking resemblance in size and distribution. Live cell imaging visualized that the uptake of ADSC-EVs preferentially took place at the SC processes from which the EVs were transported towards the nucleus. This study provided first evidence for an endocytosis mediated internalization of ADSC-EVs by SCs and underlines the therapeutic potential of ADSC-EVs in future approaches for nerve regeneration.

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Adipose Stem Cell-Based Therapeutic Targeting of Residual Androgens in African Americans with Metastatic Prostate Cancer

10.21236/ada571627 ◽

2012 ◽

Author(s):

Asim B. Abdel-Mageed

Keyword(s):

Prostate Cancer ◽

Stem Cell ◽

African Americans ◽

Metastatic Prostate Cancer ◽

Adipose Stem Cell ◽

Therapeutic Targeting

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Human Umbilical Cord Mesenchymal Stem Cell-Derived microRNA-30c-5p-Containing Extracellular Vesicles Alleviates Inflammatory Response of Diabetic Retinopathy Through Modulating the PLCG1/PKC/NF-κB Axis

SSRN Electronic Journal ◽

10.2139/ssrn.3514623 ◽

2020 ◽

Author(s):

Li Huang ◽

Jie Chen ◽

Xiaorong Gao ◽

Yujiao Dan ◽

Jinhua Gan ◽

...

Keyword(s):

Diabetic Retinopathy ◽

Stem Cell ◽

Mesenchymal Stem Cell ◽

Inflammatory Response ◽

Umbilical Cord ◽

Extracellular Vesicles ◽

Human Umbilical Cord

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Human-Induced Pluripotent Stem-Cell-Derived Smooth Muscle Cells Increase Angiogenesis to Treat Hindlimb Ischemia

Cells ◽

10.3390/cells10040792 ◽

2021 ◽

Vol 10 (4) ◽

pp. 792

Author(s):

Xixiang Gao ◽

Mingjie Gao ◽

Jolanta Gorecka ◽

John Langford ◽

Jia Liu ◽

...

Keyword(s):

Stem Cells ◽

Smooth Muscle ◽

Stem Cell ◽

Smooth Muscle Cells ◽

Functional Outcomes ◽

Ethical Issues ◽

Muscle Cells ◽

Doppler Imaging ◽

Hindlimb Ischemia ◽

Induced Pluripotent

Induced pluripotent stem cells (iPSC) represent an innovative, somatic cell-derived, easily obtained and renewable stem cell source without considerable ethical issues. iPSC and their derived cells may have enhanced therapeutic and translational potential compared with other stem cells. We previously showed that human iPSC-derived smooth muscle cells (hiPSC-SMC) promote angiogenesis and wound healing. Accordingly, we hypothesized that hiPSC-SMC may be a novel treatment for human patients with chronic limb-threatening ischemia who have no standard options for therapy. We determined the angiogenic potential of hiPSC-SMC in a murine hindlimb ischemia model. hiPSC-SMC were injected intramuscularly into nude mice after creation of hindlimb ischemia. Functional outcomes and perfusion were measured using standardized scores, laser Doppler imaging, microCT, histology and immunofluorescence. Functional outcomes and blood flow were improved in hiPSC-SMC-treated mice compared with controls (Tarlov score, p < 0.05; Faber score, p < 0.05; flow, p = 0.054). hiPSC-SMC-treated mice showed fewer gastrocnemius fibers (p < 0.0001), increased fiber area (p < 0.0001), and enhanced capillary density (p < 0.01); microCT showed more arterioles (<96 μm). hiPSC-SMC treatment was associated with fewer numbers of macrophages, decreased numbers of M1-type (p < 0.05) and increased numbers of M2-type macrophages (p < 0.0001). Vascular endothelial growth factor (VEGF) expression in ischemic limbs was significantly elevated with hiPSC-SMC treatment (p < 0.05), and inhibition of VEGFR-2 with SU5416 was associated with fewer capillaries in hiPSC-SMC-treated limbs (p < 0.0001). hiPSC-SMC promote VEGF-mediated angiogenesis, leading to improved hindlimb ischemia. Stem cell therapy using iPSC-derived cells may represent a novel and potentially translatable therapy for limb-threatening ischemia.

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