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      Clinical application of a double-modified sulfated bacterial cellulose scaffold material loaded with FGFR2-modified adipose-derived stem cells in urethral reconstruction

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          Abstract

          Background

          Urethral stricture and reconstruction are one of the thorny difficult problems in the field of urology. The continuous development of tissue engineering and biomaterials has given new therapeutic thinking to this problem. Bacterial cellulose (BC) is an excellent biomaterial due to its accessibility and strong plasticity. Moreover, adipose-derived stem cells (ADSCs) could enhance their wound healing ability through directional modification.

          Methods

          First, we used physical drilling and sulfonation in this study to make BC more conducive to cell attachment and degradation. We tested the relevant mechanical properties of these materials. After that, we attached Fibroblast Growth Factor Receptor 2 (FGFR2)-modified ADSCs to the material to construct a urethra for tissue engineering. Afterward, we verified this finding in the male New Zealand rabbit model and carried out immunohistochemical and imaging examinations 1 and 3 months after the operation. At the same time, we detected the potential biological function of FGFR2 by bioinformatics and a cytokine chip.

          Results

          The results show that the composite has excellent repairability and that this ability is correlated with angiogenesis. The new composite in this study provides new insight and therapeutic methods for urethral reconstruction. The preliminary mechanism showed that FGFR2 could promote angiogenesis and tissue repair by promoting the secretion of Vascular Endothelial Growth Factor A (VEGFA) from ADSCs.

          Conclusions

          Double-modified sulfonated bacterial cellulose scaffolds combined with FGFR2-modified ADSCs provide new sight and treatments for patients with urethral strictures.

          Supplementary Information

          The online version contains supplementary material available at 10.1186/s13287-022-03164-9.

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          Most cited references38

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          clusterProfiler 4.0: A universal enrichment tool for interpreting omics data

          Summary Functional enrichment analysis is pivotal for interpreting high-throughput omics data in life science. It is crucial for this type of tool to use the latest annotation databases for as many organisms as possible. To meet these requirements, we present here an updated version of our popular Bioconductor package, clusterProfiler 4.0. This package has been enhanced considerably compared with its original version published 9 years ago. The new version provides a universal interface for functional enrichment analysis in thousands of organisms based on internally supported ontologies and pathways as well as annotation data provided by users or derived from online databases. It also extends the dplyr and ggplot2 packages to offer tidy interfaces for data operation and visualization. Other new features include gene set enrichment analysis and comparison of enrichment results from multiple gene lists. We anticipate that clusterProfiler 4.0 will be applied to a wide range of scenarios across diverse organisms.
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            Bacterial cellulose production, properties and applications with different culture methods – A review

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              Hopes and Limits of Adipose-Derived Stem Cells (ADSCs) and Mesenchymal Stem Cells (MSCs) in Wound Healing

              Adipose tissue derived stem cells (ADSCs) are mesenchymal stem cells identified within subcutaneous tissue at the base of the hair follicle (dermal papilla cells), in the dermal sheets (dermal sheet cells), in interfollicular dermis, and in the hypodermis tissue. These cells are expected to play a major role in regulating skin regeneration and aging-associated morphologic disgraces and structural deficits. ADSCs are known to proliferate and differentiate into skin cells to repair damaged or dead cells, but also act by an autocrine and paracrine pathway to activate cell regeneration and the healing process. During wound healing, ADSCs have a great ability in migration to be recruited rapidly into wounded sites added to their differentiation towards dermal fibroblasts (DF), endothelial cells, and keratinocytes. Additionally, ADSCs and DFs are the major sources of the extracellular matrix (ECM) proteins involved in maintaining skin structure and function. Their interactions with skin cells are involved in regulating skin homeostasis and during healing. The evidence suggests that their secretomes ensure: (i) The change in macrophages inflammatory phenotype implicated in the inflammatory phase, (ii) the formation of new blood vessels, thus promoting angiogenesis by increasing endothelial cell differentiation and cell migration, and (iii) the formation of granulation tissues, skin cells, and ECM production, whereby proliferation and remodeling phases occur. These characteristics would be beneficial to therapeutic strategies in wound healing and skin aging and have driven more insights in many clinical investigations. Additionally, it was recently presented as the tool key in the new free-cell therapy in regenerative medicine. Nevertheless, ADSCs fulfill the general accepted criteria for cell-based therapies, but still need further investigations into their efficiency, taking into consideration the host-environment and patient-associated factors.
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                Author and article information

                Contributors
                zhengyudong@mater.ustb.edu.cn
                linjianbj@163.com
                zhoulqmail@sina.com
                Journal
                Stem Cell Res Ther
                Stem Cell Res Ther
                Stem Cell Research & Therapy
                BioMed Central (London )
                1757-6512
                6 September 2022
                6 September 2022
                2022
                : 13
                : 463
                Affiliations
                [1 ]GRID grid.411472.5, ISNI 0000 0004 1764 1621, Department of Urology, , Peking University First Hospital, ; Beijing, 100034 China
                [2 ]GRID grid.11135.37, ISNI 0000 0001 2256 9319, Institution of Urology, , Peking University, ; Beijing, 100034 China
                [3 ]GRID grid.69775.3a, ISNI 0000 0004 0369 0705, University of Science and Technology, Beijing, ; Beijing, 100083 China
                [4 ]Beijing Key Laboratory of Urogenital Diseases (Male) Molecular Diagnosis and Treatment Center, Beijing, 100034 China
                [5 ]GRID grid.412679.f, ISNI 0000 0004 1771 3402, Department of Urology, , The First Affiliated Hospital of Anhui Medical University, ; Hefei, 230000 China
                [6 ]Cellular Biomedicine Group Inc. (CBMG), Shanghai, 200234 China
                Author information
                http://orcid.org/0000-0003-3476-5792
                Article
                3164
                10.1186/s13287-022-03164-9
                9450280
                36068613
                d9c4f804-0239-461f-8112-ccbcc9d5f53f
                © The Author(s) 2022

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

                History
                : 2 June 2022
                : 18 August 2022
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100001809, National Natural Science Foundation of China;
                Award ID: 82070704
                Award ID: 51973018
                Award ID: 51773018
                Award ID: 81670617
                Funded by: FundRef http://dx.doi.org/10.13039/501100009592, Beijing Municipal Science and Technology Commission;
                Award ID: Z191100002019017
                Award ID: Z171100001017093
                Categories
                Research
                Custom metadata
                © The Author(s) 2022

                Molecular medicine
                urethral reconstruction,bacterial cellulose,adipose-derived stem cell,sulfonated,angiogenesis

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