Endothelial progenitor cell derived exosomes mediated miR-182-5p delivery accelerate diabetic wound healing via down-regulating PPARG.

Diabetic wound is one of the most common and serious complications of diabetes, which is characterized by abnormal number and quality of wound repair related cells. Previous studies have shown that human endothelial progenitor cells derived exosomes (EPCs-EXO) can promote diabetic wound healing through modulating vascular endothelial cell function. The purpose of this study was to investigate the biological effects and molecular mechanisms of EPCs-EXO on diabetic wound healing. The regulation of EPCs-EXO on human immortalized epidermal cell line HaCaT in high glucose (HG) environment was evaluated. Our data showed that EPCs-EXO promoted the proliferation, migration, while inhibited apoptosis of HaCaTs challenged by HG via elevating miR-182-5p expression level in vitro. Skin wound healing was significantly enhanced by EPCs-EXO in diabetic mice. Moreover, bioinformatics analyses and luciferase reporter assay indicated that exosomal miR-182-5p was bound to PPARG 3' UTR sequence and inhibited the expression of PPARG. Collectively, our findings provided a new role of EPCs-EXO in the clinical treatment of diabetic skin wounds. Diabetic wound is one of the most common and serious complications of diabetes, which is characterized by abnormal number and quality of wound repair related cells. Previous studies have shown that human endothelial progenitor cells derived exosomes (EPCs-EXO) can promote diabetic wound healing through modulating vascular endothelial cell function. The purpose of this study was to investigate the biological effects and molecular mechanisms of EPCs-EXO on diabetic wound healing. The regulation of EPCs-EXO on human immortalized epidermal cell line HaCaT in high glucose (HG) environment was evaluated. Our data showed that EPCs-EXO promoted the proliferation, migration, while inhibited apoptosis of HaCaTs challenged by HG via elevating miR-182-5p expression level in vitro. Skin wound healing was significantly enhanced by EPCs-EXO in diabetic mice. Moreover, bioinformatics analyses and luciferase reporter assay indicated that exosomal miR-182-5p was bound to PPARG 3' UTR sequence and inhibited the expression of PPARG. Collectively, our findings provided a new role of EPCs-EXO in the clinical treatment of diabetic skin wounds.

DPA promotes hBMSCs osteogenic differentiation by miR-9-5p/ERK/ALP signaling pathway.

Docosahexaenoic acid (DHA) has been reported potentiate osteogenic differentiation, while Docosapentaenoic acid (DPA), another Omega-3 fatty acid, its contribution to the osteogenic differentiation of human bone-marrow-derived mesenchymal stromal cells (hBMSCs) is not entirely elucidated. The Alizarin Red S (ARS) staining and the expression of osteogenesis­associated genes were analyzed during osteogenic induction by DPA. Then, bioinformatics analysis and dual luciferase reporter assays were investigated to confirm the interactions between miR-9-5p and alkaline phosphatase (ALP). miR-9-5p mimics / inhibitor were transfected to human hBMSCs and the osteogenic assay above was also performed. Furthermore, DPA significantly promoted the phosphorylation of ERK via miR-9-5p. PD98059, a highly specific and potent ERK1/2 inhibitor, inhibited the activation of ALP and partially reversed the role of DPA during osteogenic differentiation. These data indicated that DPA promoted osteogenic differentiation of hBMSCs potentially through miR-9-5p/ERK/ALP signaling pathway, providing a potentially useful therapeutic strategy for patients to improve bone loss.

Chondrogenic differentiation of mesenchymal stem cells through cartilage matrix-inspired surface coatings.

The stem cell niche comprises soluble molecules and extracellular matrix components which provide chemical and mechanical cues that determine the differentiation of stem cells. Here, the effect of polyelectrolyte multilayer (PEM) composition and terminal layer fabricated with layer-by-layer technique (LBL) pairing either hyaluronan [in its native (nHA) and oxidized form (oHA)] or chondroitin sulfate (CS) with type I collagen (Col I) is investigated on chondrogenic differentiation of human umbilical mesenchymal stem cells (hUC-MSCs). Physical studies performed to investigate the establishment and structure of the surface coatings show that PEM composed of HA and Col I show a dominance of nHA or oHA with considerably lesser organization of Col I fibrils. In contrast, distinguished fibrilized Col I is found in nCS-containing PEM. Generally, Col I-terminated PEM promote the adhesion, migration, and growth of hUC-MSCs more than GAG-terminated surfaces due to the presence of fibrillar Col I but show a lower degree of differentiation towards the chondrogenic lineage. Notably, the Col I/nHA PEM not only supports adhesion and growth of hUC-MSCs but also significantly promotes cartilage-associated gene and protein expression as found by histochemical and molecular biology studies, which is not seen on the Col I/oHA PEM. This is related to ligation of HA to the cell receptor CD44 followed by activation of ERK/Sox9 and noncanonical TGF-ß signaling-p38 pathways that depends on the molecular weight of HA as found by immune histochemical and western blotting. Hence, surface coatings on scaffolds and other implants by PEM composed of nHA and Col I may be useful for programming MSC towards cartilage regeneration.

Host-Guest Complexation-Induced Aggregation Based on Pyrene-Modified Cyclodextrins for Improved Electronic Circular Dichroism and Circularly Polarized Luminescence.

Several γ-cyclodextrin (CD) derivatives mono- or di-substituted by pyrenes at the primary rim of the CD were demonstrated to aggregate into nano-strips in aqueous solutions, with the pyrene moieties interpenetrating into γ-CD cavities. The hydrophobic complexation-induced aggregation provides a rigid chiral environment for the pyrenes and leads to significant electronic circular dichroism (ECD) and circularly polarized luminescence (CPL) activities, giving unprecedently high gabs and glum values up to 4.3×10-2 and 5.3×10-2 , respectively. The aggregates lead to excimer emission with high quantum yields and show BCPL and BiCPL up to 338. 6 M-1 cm-1 and 169.3 M-1 cm-1 , respectively.