• 2015-10-06

    Therapeutic lymphangiogenesis using stem cell and VEGF-C hydrogel

    요약 : 
    Lymphedema is a manifestation of lymphatic system insufficiency. It arises from primary lymphatic dysplasia or secondary obliteration after lymph node dissection or irradiation. Although improvement of swelling can be achieved by comprehensive non-operative therapy, treatment of this condition requires lifelong care and good compliance. Recently molecular-based treatments using VEGF-C have been investigated by several researchers. We designed the present study to determine whether the therapeutic efficacy of implanted human adipose-derived stem cells (hADSCs) could be improved by applying a gelatin hydrogel containing VEGF-C (VEGF-C hydrogel) to the site of tissue injury in a lymphedema mouse model. Four weeks after the operation, we evaluated edema and determined lymphatic vessel density at various post-operative time points. Mice treated with hADSCs and VEGF-C hydrogel showed a significantly decreased dermal edema depth compared to the groups of mice that received hADSCs only or VEGF-C hydrogel only. Immunohistochemical analysis also revealed that the hADSC/VEGF-C hydrogel group showed significantly greater lymphatic vessel regeneration than all the other groups. hADSCs were detected in the implantation sites of all mice in the hADSC/VEGF-C group, and exhibited a lymphatic endothelial differentiation phenotype as determined by co-staining PKH-labeled hADSCs for the lymphatic marker LYVE-1. Our results suggest that co-administration of hADSCs and VEGF-C hydrogel has a substantial positive effect on lymphangiogenesis

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    • 2015-10-06

    Amniotic membrane extract-loaded double-layered wound dressing: evaluation of gel properties and wound healing

    요약 : 
    The conservative single-layered wound dressing system is decomposed when mixed in polyvinyl alcohol (PVA) solution, which means it cannot be used with a temperature-sensitive drug. The goal of this investigation was to make an amniotic membrane extract (AME)-loaded double-layered wound dressing with an improved healing result compared to the conservative single-layered wound dressing systems. The double-layered wound dressing was developed with PVA/sodium alginate using a freeze–melting technique; one layer was PVA layer and the other was the drug-loaded sodium alginate layer. Its gel properties were assessed compared to single-layered wound dressings. Moreover, in vivo wound-healing effects and histopathology were calculated compared to commercial products. The double-layered wound dressing gave a similar gel fraction and Young’s module as single-layered wound bandages developed with only PVA, and a similar inflammation ability and WVTR as single-layered wound dressings developed with PVA and sodium alginate. Our data indicate that these double-layered wound bandages were just as swellable, but more elastic and stronger than single-layered wound dressings comprised of the same polymers and quantities, possibly giving an acceptable level of moisture and accumulation of exudates in the wound zone. Compared to the commercial product, the double-layered wound dressing comprising 6.7% PVA, 0.5% sodium alginate and 0.01% AME significantly enhanced the wound-healing effect in the wound-healing test. Histological investigations showed that superior full-thickness wound-healing effects compared to the commercial product. Therefore, the double-layered wound dressing would be an outstanding wound-dressing system with improved wound healing and good gel property

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    • 2015-10-06

    Anti-Wrinkle Effects of Adipose Tissue-Derived Mesenchymal Stem Cells in a UV-Irradiated Hairless Mouse Model

    요약 : 
    The potential anti-wrinkle effects of adipose tissue-derived mesenchymal stem cells (AdMSCs) have recently been reported. In the present study, we demonstrated a protective effect of AdMSCs in a UV irradiationinduced
    hairless mouse wrinkle model. Mice treated with AdMSCs showed improvements in skin erythema index, moisture capacity and transepidermal water loss. The AdMSC-treated mice showed reduced wrinkle area, as measured by gross observation and replica image analysis, and had a thinner epidermis and increased collagen and elastic fiber content, compared with the control group, as measured by histopathological examination. These results suggested that AdMSCs may be effective in the treatment of wrinkles. The activity of AdMSCs was further confirmed by the reduction in MMP-3 mRNA expression in the skin of the AdMSC treated animals, which suggests that AdMSCs can protect the collagen from degradation induced by UV irradiation. Further studies will investigate detailed mechanisms of action of AdMSCs, with particular focus on AdMSC-derived secretory factors

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    • 2015-10-06

    Anti-wrinkle Effect of AdMSCs-CM in Photoaging Skin Model of Hairless Mice

    요약 : 
    The purpose of this study was to investigate the anti-wrinkle effect of adipose-derived mesenchymal stem cell-conditioned medium (AdMSCs-
    CM) in a UVB irradiation-induced hairless mouse wrinkle model. Mice treated with AdMSCs-CM showed improvements in transepidermal water loss (TEWL), water capacity and erythema index of skin. The AdMSCs-CM treated mice showed reduced total wrinkle area, number, length and depth, as measured by gross observation and replica image analysis, and had a thinner epidermis and increased collagen and elastic fiber content, compared with the UV control group, as measured by histopathological examination. The activity of AdMSCs-CM was further confirmed by the reduction in MMP-3 mRNA expression and MMP-2, 9 protein activity in the skin of the AdMSCs CM treated animals. These results suggested that AdMSCs-CM may be effective in the treatment of wrinkles by protecting of the collagen from degradation induced by UV irradiation. Further studies about detailed mechanisms of action of AdMSCs-CM will be needed

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    • 2015-10-06

    Epithelial to mesenchymal transition enhances the cardioprotective capacity of human amniotic epithelial cells

    요약 : 
    The amniotic epithelium consists of cells exhibiting mature epithelial cell characteristics, but also varying degrees of stemness. We tested the hypothesis that induction of epithelial-to-mesenchymal transition (EMT) in
    amniotic epithelial cells (AECs) derived from human placenta enhances their capacity to support the ischemic myocardium. In response to incubation with transforming growth factor-b1 (TGF-b1) protein, AECs lost their
    cobblestone morphology and acquired a fibroblastoid shape, associated with downregulation of E-cadherin, upregulation of N-cadherin, Akt phosphorylation, and intracellular periostin translocation. EMT–AECs displayed greatly enhanced mobility and secreted gelatinase activity compared with naive AECs. The surface presentation of CD105 and CD73 decreased, and RNA microarray analysis mirrored the loss of epithelial characteristics and transcriptional profile. Unmodified AECs and EMT–AECs were then injected intramyocardially in fully immunocompetent mice after permanent LAD ligation, and heart function was followed by MRI as well as 2D speckle tracking echocardiography after 4 weeks. EMT–AEC-treated infarct hearts displayed better global systolic function and improved longitudinal strain rate in the area of interest. Although no signals of human cells were detectable by histology, infarct size was smaller in EMT–AEC-treated hearts, associated with fewer TUNEL-positive cells and upregulation of periostin, while blood vessel density was increased in both ACE- and EMT–AEC-treated hearts. We conclude that EMT enhances the cardioprotective effects of human AECs

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    • 2015-10-06

    Healthspan-Extending Activity of Human Amniotic Membrane- and Adipose Tissue-Derived Stem Cells in F344 Rats. Stem Cells Translational Medicine

    요약 : 
    Ageing brings about the progressive decline in cognitive function and physical activity, along with losses of stem cell population and function. Although transplantation of muscle derived stem/progenitor cells extended healthspan and lifespan of progeria mice, such effects in normal animals were not confirmed. Human amniotic membrane-derived mesenchymal stem cells (AMMSCs) or adipose tissue-derived mesenchymal stem cells (ADMSCs) (1 × 106 55 cells/rat) were intravenously transplanted to 10-month-old male F344 rats once a month for their life-long periods. Transplantation of AMMSCs and ADMSCs improved cognitive and physical functions of naturally-ageing rats, extending lifespan by 23.4% and 31.3%, respectively. The stem cell therapy increased the concentration of acetylcholine, and recovered neurotrophic factors in the brain and muscles, leading to restoration of microtubule-associated protein 2, cholinergic and dopaminergic nervous systems, microvessels, muscle mass as well as antioxidative capacity. The results indicate that repeated transplantation of AMMSCs and ADMSCs elongate both healthspan and lifespan, which could be a starting point for anti-ageing or rejuvenation effects of allogeneic or autologous stem cells with minimum immune rejection.

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