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      Dermal exosomes containing miR-218-5p promote hair regeneration by regulating β-catenin signaling

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          Abstract

          Exosomes derived from dermal papilla spheroids express a high level of miR-218-5p, which directly regulates hair regeneration.

          Abstract

          The progression in the hair follicle cycle from the telogen to the anagen phase is the key to regulating hair regrowth. Dermal papilla (DP) cells support hair growth and regulate the hair cycle. However, they gradually lose key inductive properties upon culture. DP cells can partially restore their capacity to promote hair regrowth after being subjected to spheroid culture. In this study, results revealed that DP spheroids are effective at inducing the progression of the hair follicle cycle from telogen to anagen compared with just DP cell or minoxidil treatment. Because of the importance of paracrine signaling in this process, secretome and exosomes were isolated from DP cell culture, and their therapeutic efficacies were investigated. We demonstrated that miR-218-5p was notably up-regulated in DP spheroid–derived exosomes. Western blot and immunofluorescence imaging were used to demonstrate that DP spheroid–derived exosomes up-regulated β-catenin, promoting the development of hair follicles.

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          Inhalation of lung spheroid cell secretome and exosomes promotes lung repair in pulmonary fibrosis

          Idiopathic pulmonary fibrosis (IPF) is a fatal and incurable form of interstitial lung disease in which persistent injury results in scar tissue formation. As fibrosis thickens, the lung tissue loses the ability to facilitate gas exchange and provide cells with needed oxygen. Currently, IPF has few treatment options and no effective therapies, aside from lung transplant. Here we present a series of studies utilizing lung spheroid cell-secretome (LSC-Sec) and exosomes (LSC-Exo) by inhalation to treat different models of lung injury and fibrosis. Analysis reveals that LSC-Sec and LSC-Exo treatments could attenuate and resolve bleomycin- and silica-induced fibrosis by reestablishing normal alveolar structure and decreasing both collagen accumulation and myofibroblast proliferation. Additionally, LSC-Sec and LSC-Exo exhibit superior therapeutic benefits than their counterparts derived from mesenchymal stem cells in some measures. We showed that an inhalation treatment of secretome and exosome exhibited therapeutic potential for lung regeneration in two experimental models of pulmonary fibrosis.
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            Glucose-responsive insulin patch for the regulation of blood glucose in mice and minipigs

            Glucose-responsive insulin delivery systems that mimic pancreatic endocrine function could enhance health and improve quality of life for people with type 1 and type 2 diabetes with reduced β-cell function. However, insulin delivery systems with rapid in vivo glucose-responsive behaviour typically have limited insulin-loading capacities and cannot be manufactured easily. Here, we show that a single removable transdermal patch, bearing microneedles loaded with insulin and a non-degradable glucose-responsive polymeric matrix, and fabricated via in situ photopolymerization, regulated blood glucose in insulin-deficient diabetic mice and minipigs (for minipigs >25kg, glucose regulation lasted >20h with patches of ~5 cm 2 ). Under hyperglycaemic conditions, phenylboronic acid units within the polymeric matrix reversibly form glucose-boronate complexes that–owing to their increased negative charge–induce the swelling of the polymeric matrix and weaken the electrostatic interactions between the negatively charged insulin and polymers, promoting the rapid release of insulin. This proof-of-concept demonstration may aid the development of other translational stimuli-responsive microneedle patches for drug delivery.
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              Molecular principles of hair follicle induction and morphogenesis.

              Hair follicle (HF) development is the result of neuroectodermal-mesodermal interactions, and can be divided into morphologically distinguishable stages (induction, organogenesis and cytodifferentiation). The spacing, polarity and differentiation patterns of HFs are driven by interacting, self-assembling gradients of inhibitors and activators, which are established jointly by the skin epithelium and mesenchyme. For HF development to occur, the dominant-negative influence of inhibitors of the HF differentiation pathway must be locally counteracted by specific antagonists and/or overriden by stimulators of hair placode formation. Once a mesenchymal condensate of inductive fibroblasts has formed, it takes over control of most subsequent steps of HF organogenesis and of epithelial stem cell differentiation into distinct lineages. In this review we introduce the morphological characteristics, major underlying principles and molecular key players that control HF development. The focus is on recent insights into the molecular interactions leading to hair follicle induction, and we close with synthesizing a corresponding working hypothesis.
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                Author and article information

                Journal
                Sci Adv
                Sci Adv
                SciAdv
                advances
                Science Advances
                American Association for the Advancement of Science
                2375-2548
                July 2020
                24 July 2020
                : 6
                : 30
                : eaba1685
                Affiliations
                [1 ]Department of Molecular Biomedical Sciences and Comparative Medicine Institute, North Carolina State University, Raleigh, NC 27607, USA.
                [2 ]Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, and North Carolina State University, Raleigh, NC 27606, USA.
                Author notes
                [* ]Corresponding author. Email: kcheng3@ 123456ncsu.edu
                Author information
                http://orcid.org/0000-0002-8570-3439
                http://orcid.org/0000-0001-9751-0864
                http://orcid.org/0000-0001-6364-7627
                http://orcid.org/0000-0002-9355-7224
                http://orcid.org/0000-0001-7888-0763
                http://orcid.org/0000-0001-6971-101X
                http://orcid.org/0000-0002-8969-6256
                http://orcid.org/0000-0001-8053-7059
                Article
                aba1685
                10.1126/sciadv.aba1685
                7439409
                32832660
                4e8f116d-b4e4-4f22-90a2-fe81b4eaba59
                Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).

                This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial license, which permits use, distribution, and reproduction in any medium, so long as the resultant use is not for commercial advantage and provided the original work is properly cited.

                History
                : 14 January 2020
                : 11 June 2020
                Funding
                Funded by: doi http://dx.doi.org/10.13039/100000002, National Institutes of Health;
                Award ID: R01 HL123920, HL137093, HL144002, and HL146153
                Funded by: doi http://dx.doi.org/10.13039/100000968, American Heart Association;
                Award ID: 18TPA34230092 and 19EIA34660286
                Categories
                Research Article
                Research Articles
                SciAdv r-articles
                Cell Biology
                Life Sciences
                Cell Biology
                Custom metadata
                Kyle Solis

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