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      Acceleration of burn wound healing by micronized amniotic membrane seeded with umbilical cord-derived mesenchymal stem cells

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          Abstract

          Umbilical cord-derived mesenchymal stem cells (UC-MSC) are promising candidates for wound healing. However, the low amplification efficiency of MSC in vitro and their low survival rates after transplantation have limited their medical application. In this study, we fabricated a micronized amniotic membrane (mAM) as a microcarrier to amplify MSC in vitro and used mAM and MSC (mAM-MSC) complexes to repair burn wounds. Results showed that MSC could live and proliferate on mAM in a 3D culture system, exhibiting higher cell activity than in 2D culture. Transcriptome sequencing of MSC showed that the expression of growth factor-related, angiogenesis-related, and wound healing-related genes was significantly upregulated in mAM-MSC compared to traditional 2D-cultured MSC, which was verified via RT-qPCR. Gene ontology (GO) analysis of differentially expressed genes (DEGs) showed significant enrichment of terms related to cell proliferation, angiogenesis, cytokine activity, and wound healing in mAM-MSC. In a burn wound model of C57BL/6J mice, topical application of mAM-MSC significantly accelerated wound healing compared to MSC injection alone and was accompanied by longer survival of MSC and greater neovascularization in the wound.

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          Highlights

          • •

            A micronized amniotic membrane was fabricated as a microcarrier to amplify MSC ​ in vitro.

          • •

            Micronized amniotic membrane could improve the survival time and therapeutic functions of MSC ​ in vivo.

          • •

            Micronized amniotic membrane seeded with MSC greatly accelerated burn wound healing.

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          Wound repair and regeneration.

          Geoffrey C Gurtner, Sabine Werner, Yann Barrandon … (2008)
          The repair of wounds is one of the most complex biological processes that occur during human life. After an injury, multiple biological pathways immediately become activated and are synchronized to respond. In human adults, the wound repair process commonly leads to a non-functioning mass of fibrotic tissue known as a scar. By contrast, early in gestation, injured fetal tissues can be completely recreated, without fibrosis, in a process resembling regeneration. Some organisms, however, retain the ability to regenerate tissue throughout adult life. Knowledge gained from studying such organisms might help to unlock latent regenerative pathways in humans, which would change medical practice as much as the introduction of antibiotics did in the twentieth century.
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            Therapeutic targeting of the angiopoietin–TIE pathway

            Pipsa Saharinen, Lauri Eklund, Kari Alitalo (2017)
            The angiopoietin (ANG)–TIE growth factor receptor pathway regulates pathological vascular remodelling during inflammation, tumour angiogenesis and metastasis. It has become an attractive pharmacological target for oncological and ophthalmological indications, as well as sepsis, diabetic vasculopathies, organ transplantation and atherosclerosis. Here, Alitalo and colleagues provide an overview of the biology of the ANG–TIE pathway and discuss the development of therapeutics that target it.
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              Human umbilical cord mesenchymal stem cell exosomes enhance angiogenesis through the Wnt4/β-catenin pathway.

              Bin Zhang, Xiaodan Wu, Xu Zhang … (2015)
              Human umbilical cord mesenchymal stem cells (hucMSCs) and their exosomes have been considered as potential therapeutic tools for tissue regeneration; however, the underlying mechanisms are still not well understood. In this study, we isolated and characterized the exosomes from hucMSCs (hucMSC-Ex) and demonstrated that hucMSC-Ex promoted the proliferation, migration, and tube formation of endothelial cells in a dose-dependent manner. Furthermore, we demonstrated that hucMSC-Ex promoted wound healing and angiogenesis in vivo by using a rat skin burn model. We discovered that hucMSC-Ex promoted β-catenin nuclear translocation and induced the increased expression of proliferating cell nuclear antigen, cyclin D3, N-cadherin, and β-catenin and the decreased expression of E-cadherin. The activation of Wnt/β-catenin is critical in the induction of angiogenesis by hucMSC-Ex, which could be reversed by β-catenin inhibitor ICG-001. Wnt4 was delivered by hucMSC-Ex, and the knockdown of Wnt4 in hucMSC-Ex abrogated β-catenin nuclear translocation in endothelial cells. The in vivo proangiogenic effects were also inhibited by interference of Wnt4 expression in hucMSC-Ex. Taken together, these results suggest that hucMSC-Ex-mediated Wnt4 induces β-catenin activation in endothelial cells and exerts proangiogenic effects, which could be an important mechanism for cutaneous wound healing.
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                Author and article information

                Contributors
                Yongjun Zheng
                Shichu Xiao
                Journal
                Journal ID (nlm-ta): Mater Today Bio
                Journal ID (iso-abbrev): Mater Today Bio
                Title: Materials Today Bio
                Publisher: Elsevier
                ISSN (Electronic): 2590-0064
                Publication date PMC-release: 07 June 2023
                Publication date Collection: June 2023
                Publication date (Electronic): 07 June 2023
                Volume: 20
                Electronic Location Identifier: 100686
                Affiliations
                [a ]Department of Burn Surgery, The First Affiliated Hospital of Naval Medical University, Shanghai, 200433, People's Republic of China
                [b ]Department of Obstetrics and Gynecology, Tongji Hospital, Tongji University School of Medicine, Shanghai, 200065, People's Republic of China
                Author notes
                [∗ ]Corresponding author. smmuzhengyongjun@ 123456163.com
                [∗∗ ]Corresponding author. huangzhuoxiao@ 123456sohu.com
                [1]

                These authors contributed equally to this article.

                Article
                Publisher Item ID: S2590-0064(23)00146-1 Publisher ID: 100686
                DOI: 10.1016/j.mtbio.2023.100686
                PMC ID: 10276167
                SO-VID: e092f30a-f38e-4629-b049-13d4ea73f134
                Copyright © © 2023 The Author(s)
                License:

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                Date received : 25 February 2023
                Date revision received : 11 May 2023
                Date accepted : 29 May 2023
                Categories
                Subject: Full Length Article

                Keywords: burn wound healing,microcarrier,amniotic membrane,umbilical cord-derived mesenchymal stem cells
                Data availability:
                Keywords: burn wound healing, microcarrier, amniotic membrane, umbilical cord-derived mesenchymal stem cells

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