Chronic non-healing wounds represent one of the most common complications of diabetes and need advanced treatment strategies. Exosomes are key mediators of cell paracrine action and can be directly utilized as therapeutic agents for tissue repair and regeneration. Here, we explored the effects of exosomes from human urine-derived stem cells (USC-Exos) on diabetic wound healing and the underlying mechanism.Methods: USCs were characterized by flow cytometry and multipotent differentiation potential analyses. USC-Exos were isolated from the conditioned media of USCs and identified by transmission electron microscopy and flow cytometry. A series of functional assays in vitro were performed to assess the effects of USC-Exos on the activities of wound healing-related cells. Protein profiles in USC-Exos and USCs were examined to screen the candidate molecules that mediate USC-Exos function. The effects of USC-Exos on wound healing in streptozotocin-induced diabetic mice were tested by measuring wound closure rates, histological and immunofluorescence analyses. Meanwhile, the role of the candidate protein in USC-Exos-induced regulation of angiogenic activities of endothelial cells and diabetic wound healing was assessed.Results: USCs were positive for CD29, CD44, CD73 and CD90, but negative for CD34 and CD45. USCs were able to differentiate into osteoblasts, adipocytes and chondrocytes. USC-Exos exhibited a cup- or sphere-shaped morphology with a mean diameter of 51.57 ± 2.93 nm and positive for CD63 and TSG101. USC-Exos could augment the functional properties of wound healing-related cells including the angiogenic activities of endothelial cells. USC-Exos were enriched in the proteins that are involved in regulation of wound healing-related biological processes. Particularly, a pro-angiogenic protein called deleted in malignant brain tumors 1 (DMBT1) was highly expressed in USC-Exos. Further functional assays showed that DMBT1 protein was required for USC-Exos-induced promotion of angiogenic responses of cultured endothelial cells, as well as angiogenesis and wound healing in diabetic mice.Conclusion: Our findings suggest that USC-Exos may represent a promising strategy for diabetic soft tissue wound healing by promoting angiogenesis via transferring DMBT1 protein.
We report a study of ν(μ) charged-current quasielastic events in the segmented scintillator inner tracker of the MINERvA experiment running in the NuMI neutrino beam at Fermilab. The events were selected by requiring a μ- and low calorimetric recoil energy separated from the interaction vertex. We measure the flux-averaged differential cross section, dσ/dQ², and study the low energy particle content of the final state. Deviations are found between the measured dσ/dQ² and the expectations of a model of independent nucleons in a relativistic Fermi gas. We also observe an excess of energy near the vertex consistent with multiple protons in the final state.
Two different nuclear-medium effects are isolated using a low three-momentum transfer subsample of neutrino-carbon scattering data from the MINERvA neutrino experiment. The observed hadronic energy in charged-current νµ interactions is combined with muon kinematics to permit separation of the quasielastic and ∆(1232) resonance processes. First, we observe a small cross section at very low energy transfer that matches the expected screening effect of long-range nucleon correlations. Second, additions to the event rate in the kinematic region between the quasielastic and ∆ resonance processes are needed to describe the data. The data in this kinematic region also has an enhanced population of multi-proton final states. Contributions predicted for scattering from a nucleon pair have both properties; the model tested in this analysis is a significant improvement but does not fully describe the data. We present the results as a double-differential cross section to enable further investigation of nuclear models. Improved description of the effects of the nuclear environment are required by current and future neutrino oscillation experiments.
We have isolatedνµ charged-current quasi-elastic interactions occurring in the segmented scintillator tracking region of the MINERvA detector running in the NuMI neutrino beam at Fermilab. We measure the flux-averaged differential cross-section, dσ/dQ 2 , and compare to several theoretical models of quasi-elastic scattering. Good agreement is obtained with a model where the nucleon axial mass, MA, is set to 0.99 GeV/c 2 but the nucleon vector form factors are modified to account for the observed enhancement, relative to the free nucleon case, of the cross-section for the exchange of transversely polarized photons in electron-nucleus scattering. Our data at higher Q 2 favor this interpretation over an alternative in which the axial mass is increased.
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